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PARP1 — TERF2IP

Protein-Protein interactions - manually collected from original source literature:

Studies that report less than 10 interactions are marked with *

• IRef Biogrid Interaction: PARP1 — TERF2IP (physical association, affinity chromatography technology) O'Connor et al., J Biol Chem 2004
• MIPS CORUM Rap1 complex: Rap1 complex complex (MRE11A-PARP1-RAD50-TERF2-TERF2IP-XRCC5-XRCC6) O'Connor et al., J Biol Chem 2004
• IRef Corum Interaction: Complex of PARP1-XRCC6-XRCC5-MRE11A-TERF2-RAD50-TERF2IP (association, anti tag coimmunoprecipitation) O'Connor et al., J Biol Chem 2004

Text-mined interactions from Literome

Matsubara et al., Oncogene 1999 : In COS cells, Ral GDP dissociation stimulator (RalGDS) induced Ral activation was stimulated by RasG12V or a Rap1/Ras chimera in which the N-terminal region of Rap1 was ligated to the C-terminal region of Ras but not by Rap1G12V or a Ras/Rap1 chimera in which the N-terminal region of Ras was ligated to the C-terminal region of Rap1, although RalGDS interacted with these small GTP binding proteins ... These results indicate that Ras recruits RalGDS to the plasma membrane and that the translocated RalGDS induces the activation of Ral, but that Rap1 does not activate Ral due to distinct subcellular localization ... These results indicate that Ras recruits RalGDS to the plasma membrane and that the translocated RalGDS induces the activation of Ral , but that Rap1 does not activate Ral due to distinct subcellular localization
Tsukamoto et al., J Biol Chem 1999 : Conditional SPA-1 overexpression in HeLa cells by tetracycline-regulative system suppressed Rap1 activation upon plating on dishes coated with fibronectin and resulted in the reduced adhesion ... Retroviral overexpression of SPA-1 in promyelocytic 32D cells also inhibited both activation of Rap1 and induction of cell adhesion by granulocyte colony stimulating factor without affecting differentiation ... Retroviral overexpression of SPA-1 in promyelocytic 32D cells also inhibited both activation of Rap1 and induction of cell adhesion by granulocyte colony stimulating factor without affecting differentiation
Jordan et al., J Biol Chem 1999 : Expression of chick Rap1GAP in PC-12 cells inhibited activation of Rap1 by forskolin ... Expression of chick Rap1GAP in PC-12 cells inhibited activation of Rap1 by forskolin
Okada et al., Mol Cell Biol 1999 : B-Raf carrying this mutation was not activated by Rap1A but retained its response to Ras
Mochizuki et al., Nature 1999 : This decrease in GTP bound Rap1 activates ERK/MAPK ... This decrease in GTP bound Rap1 activates ERK/MAPK
Ichiba et al., FEBS Lett 1999 : We demonstrated that GFR can activate Rap1 but not H-Ras in 293T cells and that the cdc25 domain of GFR is required for the activation of Rap1
Alsayed et al., J Immunol 2000 : This results in the IFN-gamma dependent activation of Rap1 , a protein known to exhibit tumor suppressor activity and mediate growth inhibitory responses
Palsson et al., J Biol Chem 2000 : Furthermore, constitutively active Rap1AV12 inhibited p38 MAPK activation by IL-1, consistent with Rap antagonizing Ras function ... Furthermore, constitutively active Rap1AV12 inhibited p38 MAPK activation by IL-1, consistent with Rap antagonizing Ras function
Reedquist et al., J Cell Biol 2000 : Importantly, CD31 selectively activated the small Ras related GTPase, Rap1 , but not Ras, R-Ras, or Rap2
Haendeler et al., Circ Res 2000 : Activation of ERK1/ERK2 in AT1Rwt required Ras, whereas AT1R ( Del221/222 ) required Rap1
Mochizuki et al., J Biol Chem 2000 : We have found that R-Ras, but not Rap1 , mediates JNK activation by v-Crk in 293T and NIH 3T3 cells
Annerén et al., J Biol Chem 2000 : GTK expression induces a nerve growth factor independent Rap1 activation, probably through altered CrkII signaling
Gotoh et al., J Biol Chem 2000 (Breast Neoplasms) : p130Cas regulates the activity of AND-34, a novel Ral, Rap1 , and R-Ras guanine nucleotide exchange factor ... p130Cas regulates the activity of AND-34, a novel Ral, Rap1 , and R-Ras guanine nucleotide exchange factor
McPhee et al., FEBS Lett 2000 : Challenge of Rat1 cells with rolipram alone was able to elicit the phosphorylation of CREB but not activation of either Rap1A or Rap1B
Grewal et al., J Biol Chem 2000 : This pathway involves the PKA dependent activation of the Ras related small G-protein, Rap1 , and subsequent stimulation of the neuronal Raf isoform, B-Raf
von Lintig et al., Oncogene 2000 (Second Messenger Systems) : Thus, cAMP activation of Rap 1 in HL-60 cells is likely through a cAMP regulated guanine nucleotide exchange factor ( cAMP-GEF ) and since cAMP does not activate Rap 1 in the variant cells, the data suggest that full post-translational processing of Rap 1 is necessary for cAMP-GEF activation of Rap 1
Lu et al., Exp Cell Res 2000 : We demonstrate that NGF and EGF induce Rap1 activation in PC12-Shb cells, while FGF-2 fails to do so ... We demonstrate that NGF and EGF induce Rap1 activation in PC12-Shb cells, while FGF-2 fails to do so ... However, PC12 cells expressing Shb with an inactivated SH2 domain do not respond to NGF stimulation with Rap1 activation ... The CrkII SH2 domain interacts with Shb and a 130- to 135-kDa phosphotyrosine protein present mainly in PC12-Shb cells and these interactions may thus relate to the effect of Shb on Rap1 activation ... These results suggest a role of Shb in NGF dependent Rap1 signaling and this pathway may be of significance for neurite outgrowth under certain conditions ... These results suggest a role of Shb in NGF dependent Rap1 signaling and this pathway may be of significance for neurite outgrowth under certain conditions
Xing et al., Mol Cell Biol 2000 (MAP Kinase Signaling System) : In addition, we found that Rap1 also mediates oncogenic Src signaling
York et al., Mol Cell Biol 2000 : In PC12 cells, NGF activates Ras and Rap1 to elicit the rapid and sustained activation of ERKs respectively ... We show here that Rap1 activation requires both TrkA internalization and PI3-K, whereas Ras activation requires neither TrkA internalization nor PI3-K ... We show here that Rap1 activation requires both TrkA internalization and PI3-K , whereas Ras activation requires neither TrkA internalization nor PI3-K
Gold et al., Immunol Rev 2000 : In this review, we discuss the role of phosphatidylinositol 3-kinase (PI3K) and Rap 1 in B-cell receptor (BCR) signaling ... We showed that the BCR activates Rap1 via phospholipase C-dependent production of diacylglycerol
Carey et al., Mol Cell Biol 2000 (MAP Kinase Signaling System) : CD28 inhibits Rap1 activation because it selectively stimulates an extrinsic Rap1 GTPase activity ... The ability of CD28 to stimulate Rap1 GTPase activity was dependent on the tyrosine kinase Lck ... The ability of CD28 to stimulate Rap1 GTPase activity was dependent on the tyrosine kinase Lck
Arai et al., J Biol Chem 2001 : Rap1 is activated by erythropoietin or interleukin-3 and is involved in regulation of beta1 integrin mediated hematopoietic cell adhesion ... Rap1 is activated by erythropoietin or interleukin-3 and is involved in regulation of beta1 integrin mediated hematopoietic cell adhesion ... These results suggest that Epo and IL-3 activate Rap1 at least partly through the CrkL-C3G complex as well as through additional pathways most likely involving phospholipase Cgamma and strongly implicate Rap1 in regulation of beta ( 1 ) integrin mediated hematopoietic cell adhesion ... These results suggest that Epo and IL-3 activate Rap1 at least partly through the CrkL-C3G complex as well as through additional pathways most likely involving phospholipase Cgamma and strongly implicate Rap1 in regulation of beta ( 1 ) integrin mediated hematopoietic cell adhesion
Zanassi et al., J Biol Chem 2001 : These results suggest that, in striatal neurons, intracellular Ca ( 2+ ) release, Rap1 , and ERK pathway play a crucial role in the PKA induced CREB phosphorylation and CREB dependent transcription
Pizon et al., Oncogene 2000 (MAP Kinase Signaling System) : Although the role of Rap1A in MAPK activation has been analysed in various cell types, the signalling pathways activated by Rap1A have not been explored in myogenic cells ... We provide evidence that Rap1A mutants promote ERK activation and that the active protein induces a more sustained activation than the inactive protein
Grumbach et al., Br J Haematol 2001 (Leukemia, Myelogenous, Chronic, BCR-ABL Positive) : In addition to its interaction with Stat5, CrkL interacts with C3G in KT-1 cells and such an interaction regulates the downstream activation of the small GTPase Rap1 , which also mediates inhibition of cell proliferation ... In addition to its interaction with Stat5 , CrkL interacts with C3G in KT-1 cells and such an interaction regulates the downstream activation of the small GTPase Rap1 , which also mediates inhibition of cell proliferation
Posern et al., Oncogene 2000 (MAP Kinase Signaling System) : Further characterization in COS cells showed that the CBR or a c-Crk I SH3 mutant specifically reduces both the basal as well as the stimulated Rap1 activity in a dose dependent manner, whereas Ras is not affected ... We conclude that cellular Crk/CRKL complexes, recruited to upstream signaling components, contribute to basal and bombesin induced Rap1 activity, which is independent from the Ras-Raf-Erk pathway under these circumstances ... We conclude that cellular Crk/CRKL complexes, recruited to upstream signaling components, contribute to basal and bombesin induced Rap1 activity, which is independent from the Ras-Raf-Erk pathway under these circumstances
Sawada et al., J Cell Sci 2001 (MAP Kinase Signaling System) : Rap1 is involved in cell stretching modulation of p38 but not ERK or JNK MAP kinase ... Rap1 is involved in cell stretching modulation of p38 but not ERK or JNK MAP kinase ... Furthermore, overexpression of Rap1 enhanced p38 activity but not ERK or JNK activity ... Furthermore, overexpression of Rap1 enhanced p38 activity but not ERK or JNK activity
Ohba et al., Hokkaido Igaku Zasshi 2001 : In 293T cells, Rap2 was regulated by the same set of guanine nucleotide exchange factors ( GEFs ) and GTPase activating proteins ( GAPs ) as those which regulated Rap1
Tsygankova et al., Mol Cell Biol 2001 : Both cAMP and protein kinase A (PKA) contribute to the regulation of Rap1 activity and signaling by TSH ... Interference with PKA activity blocked phosphorylation but not the activation of Rap1 ... The dual regulation of Rap1 by cAMP and PKA extends to downstream effectors ... The ability of TSH to stimulate Akt phosphorylation was markedly enhanced by the expression of activated Rap1A and was repressed in cells expressing a putative dominant negative Rap1A mutant ... Although the expression of activated Rap1A was sufficient to stimulate wortmannin-sensitive Akt phosphorylation, TSH further increased Akt phosphorylation in a phosphatidylinositol 3-kinase- and PKA dependent manner
Kievit et al., Mol Endocrinol 2001 (Pituitary Neoplasms) : These findings provide evidence for a model for cAMP induced PRL transcription involving Rap1 induced MAPK activity leading to stimulation of the transcriptional coactivators, CBP and p300
Garcia et al., Mol Cell Biol 2001 : We show that the small GTPases Ras and Rap1 contribute together to TPO induced ERK activation in UT7-Mpl cells and that they do so by activating different Raf kinases as downstream effectors : a Ras-Raf-1 pathway is required to initiate ERK activation while Rap1 sustains this signal through B-Raf ... Indeed, ( i ) in cells expressing wild-type or mutant Mpl, TPO induced Ras and Rap1 activation correlates with early and sustained phases of ERK signal, respectively ; ( ii ) interfering mutants of Ras and Rap1 both inhibit ERK kinase activity and ERK dependent Elk1 transcriptional activation in response to TPO ; ( iii ) the kinetics of activation of Raf-1 and B-Raf by TPO follow those of Ras and Rap1, respectively ; ( iv ) RasV12 mediated Elk1 activation was modulated by the wild type or interfering mutants of Raf-1 but not those of B-Raf ; ( v ) Elk1 activation mediated by a constitutively active mutant of Rap1 ( Rap1V12 ) is potentiated by B-Raf and inhibited by an interfering mutant of this kinase ... Indeed, ( i ) in cells expressing wild-type or mutant Mpl, TPO induced Ras and Rap1 activation correlates with early and sustained phases of ERK signal, respectively ; ( ii ) interfering mutants of Ras and Rap1 both inhibit ERK kinase activity and ERK dependent Elk1 transcriptional activation in response to TPO ; ( iii ) the kinetics of activation of Raf-1 and B-Raf by TPO follow those of Ras and Rap1, respectively ; ( iv ) RasV12 mediated Elk1 activation was modulated by the wild type or interfering mutants of Raf-1 but not those of B-Raf ; ( v ) Elk1 activation mediated by a constitutively active mutant of Rap1 ( Rap1V12 ) is potentiated by B-Raf and inhibited by an interfering mutant of this kinase ... Indeed, ( i ) in cells expressing wild-type or mutant Mpl, TPO induced Ras and Rap1 activation correlates with early and sustained phases of ERK signal, respectively ; ( ii ) interfering mutants of Ras and Rap1 both inhibit ERK kinase activity and ERK dependent Elk1 transcriptional activation in response to TPO ; ( iii ) the kinetics of activation of Raf-1 and B-Raf by TPO follow those of Ras and Rap1, respectively ; ( iv ) RasV12 mediated Elk1 activation was modulated by the wild type or interfering mutants of Raf-1 but not those of B-Raf ; ( v ) Elk1 activation mediated by a constitutively active mutant of Rap1 ( Rap1V12 ) is potentiated by B-Raf and inhibited by an interfering mutant of this kinase
Guo et al., J Biol Chem 2001 : Similar to other small GTP binding proteins, activation of Rap1 requires a guanine nucleotide exchange factor (GEF) to promote its conversion from the GDP- to GTP bound form
Schmitt et al., Mol Cell Biol 2001 : Activation of Rap1 by cAMP induces the association of Rap1 with Raf-1 and limits Ras dependent activation of ERK ... Activation of Rap1 by cAMP induces the association of Rap1 with Raf-1 and limits Ras dependent activation of ERK ... In NIH 3T3 cells, Rap1 is required not only for cAMP 's inhibition of ERK activation but for inhibition of cell proliferation and mitogenesis as well
Wu et al., J Neurosci 2001 (MAP Kinase Signaling System) : We investigated a role for endogenous Rap1 , a small monomeric GTP binding protein of the Ras family, in nerve growth factor (NGF) signaling in PC12 cells ... Although both epidermal growth factor (EGF) and NGF caused transient activation of Ras, only NGF induced the activation of Rap1 ... Although both epidermal growth factor (EGF) and NGF caused transient activation of Ras, only NGF induced the activation of Rap1 ... Pretreatment of PC12 cells with brefeldin A ( BFA ), which disrupts the Golgi and endosomal compartments, had little effect on Ras activation but strongly inhibited NGF induced Rap1 activation and continuing MAPK activation ... We propose that endosomes are a site from which NGF induces the prolonged activation of Rap1 and MAPK
Wang et al., J Biol Chem 2001 : Moreover, inhibition of Rap1 by a Rap1 GTPase activating protein-1 also resulted in a decrease in ERK and Akt phosphorylation, which was not further decreased by cAMP, suggesting that cAMP inhibits ERK and Akt by inhibiting Rap1 ... Moreover, inhibition of Rap1 by a Rap1 GTPase activating protein-1 also resulted in a decrease in ERK and Akt phosphorylation, which was not further decreased by cAMP, suggesting that cAMP inhibits ERK and Akt by inhibiting Rap1 ... The role of Rap1 in ERK and Akt activity was further demonstrated by our observation that an active form of Epac, which activated Rap1 in the absence of cAMP, increased ERK and Akt phosphorylation ... The role of Rap1 in ERK and Akt activity was further demonstrated by our observation that an active form of Epac, which activated Rap1 in the absence of cAMP, increased ERK and Akt phosphorylation
Gao et al., J Biol Chem 2001 : In accordance with this, RA-GEF-2 colocalizes with activated M-Ras in the plasma membrane in COS-7 cells, suggesting a role of RA-GEF-2 in the regulation of Rap1 and Rap2, particularly in the plasma membrane ... In accordance with this, RA-GEF-2 colocalizes with activated M-Ras in the plasma membrane in COS-7 cells, suggesting a role of RA-GEF-2 in the regulation of Rap1 and Rap2, particularly in the plasma membrane
Iacovelli et al., Mol Pharmacol 2001 : The Rap1 dominant negative Rap1N17 significantly reduced TSH stimulated but not insulin-like growth factor 1-stimulated ERK1/2 phosphorylation, whereas the Ras dominant negative RasN17 inhibited the effect of both agonists
Chikashige et al., Curr Biol 2001 : Our results demonstrate that S. pombe Rap1 binds to telomeres through interaction with Taz1, similar to human Rap1-TRF2, and that Taz1 mediated telomere localization of Rap1 is necessary for telomere clustering and for the successful completion of meiosis
McDermott et al., J Biol Chem 2002 : In the same manner, the inhibitory effect of Rap on the activation of p38 by IL-1 occurred at a point downstream of MyD88, IRAK, and TRAF6, since the activation of p38 MAPK by these components was inhibited by overexpressing active Rap1AV12 , while neither MKK3 nor MKK6 were affected
Linnemann et al., J Biol Chem 2002 : Furthermore, it is shown that Rap1 , which was originally identified as a Ras antagonist, can block Ras mediated RalGDS signaling only when RalGDS contains an intact RBD
Wessler et al., FASEB J 2002 (Gastrointestinal Diseases...) : B-Raf/Rap1 signaling, but not c-Raf-1/Ras, induces the histidine decarboxylase promoter in Helicobacter pylori infection
Schmitt et al., Mol Cell 2002 : We demonstrate here that PKA 's activation of Rap1 was mediated by the Rap1 guanine nucleotide exchange factor C3G, the adaptor Crk-L, the scaffold protein Cbl, and the tyrosine kinase Src ... Src was required for cAMP activation of Rap1 and the inhibition of ERKs and cell growth
Li et al., Mol Cell Biol 2002 : On the other hand, Rap1 activation could restore FAs in cells expressing FA-Csk
Lekmine et al., Biochem Biophys Res Commun 2002 : We also demonstrate that both the Tyk-2 and Jak-1 kinases are required for activation of the CrkL/Rap1 pathway, as the Type I IFN dependent GTP bound form of Rap1 is inhibited by overexpression of dominant negative Tyk-2 or Jak-1 mutants and is defective in cells lacking Tyk-2 or Jak-1 ... We also demonstrate that both the Tyk-2 and Jak-1 kinases are required for activation of the CrkL/Rap1 pathway, as the Type I IFN dependent GTP bound form of Rap1 is inhibited by overexpression of dominant negative Tyk-2 or Jak-1 mutants and is defective in cells lacking Tyk-2 or Jak-1
McLeod et al., Int Rev Immunol 2001 : In this review, we summarize our recent work showing that the B cell antigen receptor (BCR) , as well as chemokine receptors, activate Rap1 via a pathway that involves phospholipase C-dependent production of diacylglycerol ( DAG ) ... The possible identities of the DAG regulated guanine nucleotide exchange factors ( GEFs ) and GTPase activating proteins ( GAPs ) that regulate the activation of Rap1 by the BCR and chemokine receptors will be discussed
Fujita et al., J Biol Chem 2002 : cAMP stimulated Ras independent and Rap1 dependent ERK phosphorylation and cell proliferation in B-Raf expressing cells, but inhibited growth in B-Raf lacking cells
Morsi El-Kadi et al., Mech Dev 2002 : The small GTPase Rap1 is an immediate downstream target for Hoxb4 transcriptional regulation
Woulfe et al., J Biol Chem 2002 : Finally, using human platelets treated with selective inhibitors of phosphatidylinositol 3-kinase (PI3K) and mouse platelets selectively lacking the G ( beta ) ( gamma ) -activated form of his enzyme ( PI3Kgamma ), we show that G ( i ) -mediated Rap1 activation is PI3K dependent
McLeod et al., J Immunol 2002 : Moreover, blocking the activation of Rap1 and Rap2 via the expression of a Rap-specific GTPase activating protein significantly reduced the ability of B cells to migrate toward SDF-1 ... Moreover, blocking the activation of Rap1 and Rap2 via the expression of a Rap-specific GTPase activating protein significantly reduced the ability of B cells to migrate toward SDF-1 ... Moreover, blocking the activation of Rap1 and Rap2 via the expression of a Rap-specific GTPase activating protein significantly reduced the ability of B cells to migrate toward SDF-1
de Bruyn et al., J Biol Chem 2002 : In T-lymphocytes the Ras-like small GTPase Rap1 plays an essential role in stimulus induced inside-out activation of integrin LFA-1 ( alpha ( L ) beta ( 2 ) ) and VLA-4 ( alpha ( 4 ) beta ( 1 ) ) ... These findings indicate that available levels of GTP bound Rap1 are required for the direct activation of LFA-1 and VLA-4
Schmitt et al., J Biol Chem 2002 (MAP Kinase Signaling System) : Interestingly, beta-adrenergic stimulation of both Rap1 and ERKs, but not Ras and AKT, can be blocked by a Src mutant ( SrcS17A ) that is incapable of being phosphorylated and activated by PKA ... Furthermore, a Src mutant ( SrcS17D ), which mimics PKA phosphorylation at serine 17, stimulates Rap1 activation, Rap1/B-Raf association, and ERK activation but does not stimulate Ras or AKT
Eto et al., Proc Natl Acad Sci U S A 2002 : On the other hand, retroviral expression of CalDAG-GEFI , a Rap1 exchange factor identified by megakaryocyte gene profiling as a candidate integrin regulator, enhanced agonist induced activation of Rap1b and fibrinogen binding to alphaIIbbeta3 ( P < 0.01 )
Larson et al., Blood 2003 : Because activation of Rap1, an abundant small guanosine triphosphatase ( GTPase ) in platelets, contributes to integrin alpha ( IIb ) beta ( 3 ) activation, we asked whether and how GPVI signaling activates Rap1 in platelets ... Using a reconstituted system in RBL-2H3 cells, we found that GPVI mediated Rap1 activation is dependent on FcRgamma but independent of another platelet collagen receptor, alpha ( 2 ) beta ( 1 ) ... Using a reconstituted system in RBL-2H3 cells, we found that GPVI mediated Rap1 activation is dependent on FcRgamma but independent of another platelet collagen receptor, alpha ( 2 ) beta ( 1 ) ... Interestingly, GPVI mediated Rap1 activation in human platelets is largely dependent on adenosine diphosphate ( ADP ) signaling through the P2Y(12) and not the P2Y(1) receptor ... However, experiments with specific ADP receptor antagonists and platelets from knockout mice deficient in P2Y(1) or the P2Y(12) associated G-protein, Galphai ( 2 ), indicate that human and murine platelets also have a significant P2Y(12) independent component of GPVI mediated Rap1 activation
Grader-Beck et al., Blood 2003 : Increase of cAMP also inhibited activation of Rap1 mediated by TCR/CD3 plus CD28 ... Increase of cAMP also inhibited activation of Rap1 mediated by TCR/CD3 plus CD28 ... Thus, TCR plus CD28 mediated activation of ERK1/2 and PKB, cytokine production, and cell cycle progression, all of which are inhibited by cAMP, require activation of Ras but not Rap1 ... Thus, TCR plus CD28 mediated activation of ERK1/2 and PKB, cytokine production, and cell cycle progression, all of which are inhibited by cAMP, require activation of Ras but not Rap1 ... Thus, TCR plus CD28 mediated activation of ERK1/2 and PKB , cytokine production, and cell cycle progression, all of which are inhibited by cAMP, require activation of Ras but not Rap1
Enserink et al., Nat Cell Biol 2002 : We conclude that cAMP induced regulation of ERK and activation of Rap1 are independent processes
Lova et al., J Biol Chem 2003 (Second Messenger Systems) : Two unrelated inhibitors of phosphatidylinositol 3-kinase (PI3K), wortmannin and LY294002, totally prevented Rap1B activation in platelets stimulated by cross linking of FcgammaRIIA, by stimulation of the P2Y(12) receptor for ADP, or by epinephrine ... Two unrelated inhibitors of phosphatidylinositol 3-kinase (PI3K) , wortmannin and LY294002, totally prevented Rap1B activation in platelets stimulated by cross linking of FcgammaRIIA, by stimulation of the P2Y(12) receptor for ADP, or by epinephrine
Sakakibara et al., J Cell Sci 2002 : Novel function of Chat in controlling cell adhesion via Cas-Crk-C3G-pathway mediated Rap1 activation ... Novel function of Chat in controlling cell adhesion via Cas-Crk-C3G-pathway mediated Rap1 activation ... Interestingly, Chat and Cas synergistically activated Rap1 ... Certain Cas, Crk or C3G mutants suppressed Rap1 activation by Chat
Song et al., Oncogene 2002 : Differential roles of Ras and Rap1 in growth factor dependent activation of phospholipase C epsilon
Carey et al., J Biol Chem 2003 : In contrast to Raf-1, B-Raf is activated by Rap1
Gendron et al., J Biol Chem 2003 : In the present report, we demonstrate that activation of the AT(2) receptor rapidly, but transiently, activated the Rap1/B-Raf complex of signaling proteins ... To assess whether cAMP was involved in the activation of Rap1/B-Raf and neuronal differentiation induced by Ang II, NG108-15 cells were treated with stimulators or inhibitors of the cAMP pathway
Lau et al., Int J Oncol 2003 (Astrocytoma) : However, there was no correlation between tuberin expression or Rap1 overexpression and the levels of Rap1 activity in the tumors studied, suggesting that the increased Rap1 activation is not the direct result of reduced tuberin Rap1-GAP function or elevated Rap1 protein expression
Nagashima et al., Mol Biol Cell 2002 : In contrast, rap1GAPII , a negative regulator of Rap1 , did not inhibit ephrin-B1 induced membrane ruffling ... In contrast, rap1GAPII , a negative regulator of Rap1 , did not inhibit ephrin-B1 induced membrane ruffling
Yamada et al., Anticancer Res 2002 (Stomach Neoplasms) : TRF1, TRF2 and TIN2 are negative regulators of telomere length, while tankyrase and Rap1 act as positive regulators ... TRF1, TRF2 and TIN2 are negative regulators of telomere length, while tankyrase and Rap1 act as positive regulators
Ohba et al., EMBO J 2003 : Epidermal growth factor (EGF) activates Ras and Rap1 at distinct intracellular regions
Shao et al., EMBO Rep 2003 : Here, we show that Cbl deficiency results in enhanced activation of Rap1 ... Thus, Cbl negatively regulates Rap1 activation, probably through a proteolysis independent E3-ubiquitin-ligase activity of Cbl that modulates protein-protein interactions
Zhang et al., J Biol Chem 2003 : Thus, Cbl-b plays a negative role in Crk-L-C3G mediated Rap1 and LFA-1 activation in T cells
Ling et al., J Biol Chem 2003 (MAP Kinase Signaling System) : Src-CrkII-C3G dependent activation of Rap1 switches growth hormone stimulated p44/42 MAP kinase and JNK/SAPK activities ... Src-CrkII-C3G dependent activation of Rap1 switches growth hormone stimulated p44/42 MAP kinase and JNK/SAPK activities ... Activated Rap1 inhibited GH-stimulated activation of RalA and subsequent GH-stimulated p44/42 MAP kinase activity and Elk-1 mediated transcription
Alleaume et al., Neuropeptides 2003 : We also demonstrated that VIP induced phosphorylation of the small GTPase Rap1 in these cancerogenous cells ... Furthermore, VIP induced the activation of the small GTPase Rap1 and of a 95 kDa isoform of the serine/threonine kinase B-Raf
Maillet et al., Nat Cell Biol 2003 (Alzheimer Disease) : We also show that Rac activation results from activation of Rap1 through the cAMP guanine nucleotide-exchange factor (GEF) Epac1 ... We also show that Rac activation results from activation of Rap1 through the cAMP guanine nucleotide-exchange factor (GEF) Epac1
Dillon et al., J Biol Chem 2003 : Recent studies suggest that Rap1 can activate the MAP kinase kinase kinase B-Raf that is either endogenously or ectopically expressed
Berruti et al., Cell Mol Biol Incl Cyto Enzymol 2003 : CAMP activates Rap1 in differentiating mouse male germ cells : a new signaling pathway mediated by the cAMP activated exchange factor Epac ?
Quinn et al., Blood 1992 (Granulomatous Disease, Chronic) : Finally, these results show that the expression of Rap1A in the plasma membrane is not dependent on the coordinate expression of cytochrome b , despite the close association shown for these two proteins in the normal cell membrane
Nur-E-Kamal et al., Mol Biol Cell 1992 : The GAP1 ( also called Ras GAP ) is highly specific for Ras and does not stimulate the intrinsic GTPase activity of Rap1 or Rho ... In this article, we demonstrate that the NF1C , like the GAP1C, is highly specific for Ras and does not activate either Rap1 or Rho GTPases
Boettner et al., Genetics 2003 : We further show that Rap1 acts upstream of Cno, but that Rap1 , unlike Cno, is not involved in the stimulation of JNK pathway activity, indicating that Cno has both a Rap1 dependent and a Rap1 independent function in the DC process
Schulte et al., Exp Cell Res 2003 : Inhibition of phosphatidylinositol-3'-kinase (PI3K) by wortmannin inhibited adenosine A(2B) receptor mediated ERK1/2 phosphorylation and activation of Rap1 , without affecting CREB and p38 phosphorylation ... Inhibition of phosphatidylinositol-3'-kinase (PI3K) by wortmannin inhibited adenosine A(2B) receptor mediated ERK1/2 phosphorylation and activation of Rap1 , without affecting CREB and p38 phosphorylation ... Inhibition of phosphatidylinositol-3'-kinase (PI3K) by wortmannin inhibited adenosine A(2B) receptor mediated ERK1/2 phosphorylation and activation of Rap1 , without affecting CREB and p38 phosphorylation
Romano et al., J Biol Chem 2003 : Differential involvement of the Ras and Rap1 small GTPases in vasoactive intestinal and pituitary adenylyl cyclase activating polypeptides control of the prolactin gene ... By using pull-down experiments, we show that VIP and PACAP38 preferentially activate Rap1 , whereas thyrotropin releasing hormone (TRH) and epidermal growth factor (EGF) mainly activate Ras GTPase ... By using pull-down experiments, we show that VIP and PACAP38 preferentially activate Rap1 , whereas thyrotropin releasing hormone (TRH) and epidermal growth factor (EGF) mainly activate Ras GTPase ... Experiments involving the expression of the dominant negative mutants of Ras and Rap1 signaling ( RasN17 or Rap1N17 ) indicate that both GTPases Ras and Rap1 are recruited for the ERK activation by VIP and PACAP38, whereas Rap1 is poorly involved in TRH or EGF induced ERK activation ... Experiments involving the expression of the dominant negative mutants of Ras and Rap1 signaling ( RasN17 or Rap1N17 ) indicate that both GTPases Ras and Rap1 are recruited for the ERK activation by VIP and PACAP38, whereas Rap1 is poorly involved in TRH or EGF induced ERK activation ... Moreover, cotransfection of RasN17 or Rap1N17 with the PRL proximal promoter luciferase reporter construct indicates that Rap1 may be responsible for VIP/PACAP induced activation of the PRL promoter
Rong et al., J Biol Chem 2003 (MAP Kinase Signaling System) : These observations indicate that the lipase activity of PLC-gamma1 mediates NGF regulated MAPK signaling upstream of Ras/Rap1 activation probably through second messenger DAG activated Ras and Rap-GEFs
Prévost et al., Blood 2004 : From this we conclude that ( 1 ) Eph/ephrin signaling enhances the ability of platelet agonists to cause aggregation provided that those agonists can increase cytosolic Ca ( ++ ) ; ( 2 ) this is accomplished in part by activating Rap1 ; and ( 3 ) these effects require oligomerization of ephrinB1 but not phosphotyrosine based interactions with the ephrinB1 cytoplasmic domain
Baldassa et al., Brain Res Mol Brain Res 2003 (MAP Kinase Signaling System) : Moreover, protein kinase A (PKA) activity is required for depolarization induced Rap1 activation and full Erk stimulation, but is not involved in that of Ras ... This PKA dependent Rap1 activation does not require Src family kinases, but, in contrast to Ras, is sensitive to genistein, indicating the involvement of a tyrosine kinase dependent mechanism
Tiwari et al., Blood 2004 (Leukemia, Lymphocytic, Chronic, B-Cell) : Among circulating hematopoietic cells, B-CLL uniquely expresses functional EPAC1, but EPAC1 mediated Rap1 activation does not account for PDE4 inhibitor induced apoptosis ... The EPAC-specific cAMP analog 8CPT-2Me-cAMP ( 8- ( 4-chloro-phenylthio ) -2'-O-methyladenosine-3',5'-cAMP ) activates Rap1 in B-CLL cells, but, unlike rolipram/forskolin or 8-Bromo-cAMP, it does not induce PKA activation, as judged by phosphorylation of the transcription factor cAMP-response element binding protein ( CREB ) ... The EPAC-specific cAMP analog 8CPT-2Me-cAMP ( 8- ( 4-chloro-phenylthio ) -2'-O-methyladenosine-3',5'-cAMP ) activates Rap1 in B-CLL cells, but, unlike rolipram/forskolin or 8-Bromo-cAMP, it does not induce PKA activation, as judged by phosphorylation of the transcription factor cAMP-response element binding protein ( CREB )
Delcroix et al., Prog Brain Res 2004 (Nerve Degeneration) : We found that NGF induced a sustained activation of Rap1 , a small monomeric GTP binding protein of the Ras family, and that this activation occurred in early endosomes that contain key elements of Rap1/pErk1/2 pathway
Katagiri et al., J Biol Chem 2004 : In Jurkat T cells, TCR cross linking triggered persistent Rap1 activation, and SDF-1 ( CXCL12 ) activated Rap1 transiently ... Furthermore, when expressed in Jurkat cells, CalDAG-GEFI , a calcium and diacylglycerol-responsive Rap1 exchange factor, associated with Rap1, and resulted in enhanced Rap1 activation and adhesion triggered by the TCR
Huang et al., J Biol Chem 2004 (MAP Kinase Signaling System) : Rap1 induced p38 mitogen activated protein kinase activation facilitates AMPA receptor trafficking via the GDI.Rab5 complex ... Rap1 induced p38 mitogen activated protein kinase activation facilitates AMPA receptor trafficking via the GDI.Rab5 complex
Caloca et al., J Biol Chem 2004 : Finally, we show that the RasGRP2/F-actin interaction promotes the regionalized activation of Rap1 in juxtamembrane areas of the cell
Cullen et al., Am J Physiol Gastrointest Liver Physiol 2004 : Glucagon, CPT-cAMP, and CPT-2-Me-cAMP all activated Rap 1 , a downstream effector of cAMP-GEF ... Glucagon , CPT-cAMP, and CPT-2-Me-cAMP all activated Rap 1 , a downstream effector of cAMP-GEF
Ballif et al., Curr Biol 2004 : We report that Reelin stimulates tyrosine phosphorylation of C3G and activates Rap1
Lova et al., J Biol Chem 2004 : We found that, similarly to thrombin, selective stimulation of either PAR-1 or PAR-4 by specific activating peptides caused accumulation of GTP bound Rap1B in a dose dependent manner ... We found that, similarly to thrombin, selective stimulation of either PAR-1 or PAR-4 by specific activating peptides caused accumulation of GTP bound Rap1B in a dose dependent manner ... In the presence of the ADP scavengers apyrase or phosphocreatine-phosphocreatine kinase, activation of Rap1B induced by stimulation of either PAR-1 or PAR-4 was totally inhibited ... In the presence of the ADP scavengers apyrase or phosphocreatine-phosphocreatine kinase, activation of Rap1B induced by stimulation of either PAR-1 or PAR-4 was totally inhibited ... Concomitant stimulation of both PAR-1 and PAR-4 in the presence of ADP scavengers still resulted in a strongly reduced activation of Rap1B ... Concomitant stimulation of both PAR-1 and PAR-4 in the presence of ADP scavengers still resulted in a strongly reduced activation of Rap1B ... By contrast, inhibition of MAP kinases or p160ROCK , which have been shown to be activated upon thrombin binding to GPIb-IX-V, did not affect agonist induced activation of Rap1B in the presence of ADP scavengers ... By contrast, inhibition of MAP kinases or p160ROCK , which have been shown to be activated upon thrombin binding to GPIb-IX-V, did not affect agonist induced activation of Rap1B in the presence of ADP scavengers
Aoki et al., J Biol Chem 2004 (MAP Kinase Signaling System) : Rap1 , but not Ras, is activated in response to ephrin-A1
Arévalo et al., EMBO J 2004 : ARMS is rapidly tyrosine phosphorylated after binding of neurotrophins to Trk receptors and provides a docking site for the CrkL-C3G complex, resulting in Rap1 dependent sustained ERK activation
Chotani et al., Am J Physiol Heart Circ Physiol 2005 : The former effect predominates in serum stimulated VSMs leading to a COX-2, cAMP, and Rap 1-dependent increase in alpha(2C)-AR expression
Arthur et al., J Cell Biol 2004 : Rap1a activates Rac1 and requires Rac1 to enhance spreading, whereas Rac1 induces spreading independently of Rap1 ... Overexpressed VAV2 and Tiam1 specifically require Rap1 to promote spreading, even though Rac1 is activated independently of Rap1 ... Overexpressed VAV2 and Tiam1 specifically require Rap1 to promote spreading, even though Rac1 is activated independently of Rap1 ... Rap1 is necessary for the accumulation of VAV2 in membrane protrusions at the cell periphery
Shi et al., Oncogene 2004 : The ability of Rap1-AGE to inhibit C3G mediated Rap1-activation and cell spreading was also demonstrated ... The ability of Rap1-AGE to inhibit C3G mediated Rap1-activation and cell spreading was also demonstrated ... On the other hand, Rap1 activation mediated by two other GEFs, Epac and smgGDS, was not inhibited by Rap1-AGE ... On the other hand, Rap1 activation mediated by two other GEFs, Epac and smgGDS, was not inhibited by Rap1-AGE
Fukuyama et al., J Biol Chem 2005 : Involvement of the c-Src-Crk-C3G-Rap1 signaling in the nectin induced activation of Cdc42 and formation of adherens junctions ... The activation of either c-Src or Rap1 alone was insufficient for and the activation of both molecules was essential for the activation of FRG ... These results indicate that Rap1 is activated by nectins through the c-Src-Crk-C3G signaling and involved in the nectin induced, c-Src- and FRG mediated activation of Cdc42 and formation of AJs ... These results indicate that Rap1 is activated by nectins through the c-Src-Crk-C3G signaling and involved in the nectin induced, c-Src- and FRG mediated activation of Cdc42 and formation of AJs
Obara et al., J Cell Sci 2004 : In PC12 cells, Src phosphorylation on S17 participates in the activation of the small G protein Rap1 by both cAMP and NGF ... In these cells, Rap1 is required for cAMP/PKA signaling to ERKs and also for the sustained activation of ERKs by NGF ... In these cells, Rap1 is required for cAMP/PKA signaling to ERKs and also for the sustained activation of ERKs by NGF ... The activation of Rap1 by both cAMP and NGF was blocked by PP2, an inhibitor of Src family kinases, and by a Src mutant incapable of being phosphorylated by PKA ( SrcS17A ), consistent with the requirement of PKA phosphorylation of Src at S17 in these actions ... The activation of Rap1 by both cAMP and NGF was blocked by PP2 , an inhibitor of Src family kinases, and by a Src mutant incapable of being phosphorylated by PKA ( SrcS17A ), consistent with the requirement of PKA phosphorylation of Src at S17 in these actions ... The activation of Rap1 by both cAMP and NGF was blocked by PP2, an inhibitor of Src family kinases, and by a Src mutant incapable of being phosphorylated by PKA ( SrcS17A ), consistent with the requirement of PKA phosphorylation of Src at S17 in these actions ... PKA phosphorylation of Src may therefore be required for Rap1 activation in PC12 cells ... PKA phosphorylation of Src may therefore be required for Rap1 activation in PC12 cells
Mizuchi et al., Biochem Biophys Res Commun 2005 : BCR/ABL activates Rap1 and B-Raf to stimulate the MEK/Erk signaling pathway in hematopoietic cells ... BCR/ABL activates Rap1 and B-Raf to stimulate the MEK/Erk signaling pathway in hematopoietic cells ... Here we demonstrate that the inducible expression of BCR/ABL in a murine hematopoietic cell line, TonB210, leads to the activation of the Ras family small GTPase Rap1 , which is inhibited by the ABL kinase inhibitor imatinib ... Here we demonstrate that the inducible expression of BCR/ABL in a murine hematopoietic cell line, TonB210, leads to the activation of the Ras family small GTPase Rap1 , which is inhibited by the ABL kinase inhibitor imatinib ... Inhibition of Rap1 activation by a dominant negative mutant of Rap1, Rap1-N17, or SPA-1 inhibited the BCR/ABL induced activation of Elk-1
Chen et al., Mol Microbiol 2005 (MAP Kinase Signaling System) : The Rap-1 inhibitor, GGTI-298, restored MAPK activation in the presence of cAMP, further suggesting that Rap-1 is responsible for cAMP dependent MAPK inhibition
Murphy et al., Blood 2005 (Anemia, Sickle Cell) : The cAMP dependent exchange factor Epac ( exchange protein directly activated by cAMP ) is a likely upstream activator of Rap1, since Epac is present in these cells and the Epac-specific cAMP analog 8CPT-2-Me ( 8- ( 4-cholorophenylthio ) -2'-O-methyl-cAMP ) activated Rap1 and promoted SS RBC adhesion to laminin ... Surprisingly, 8CPT-2-Me activated Rap1 did not promote SS RBC adhesion to a known alpha4beta1 ligand, vascular cell adhesion molecule 1 ( VCAM-1 )
Schultess et al., Blood 2005 : The Ras-like guanine-nucleotide binding protein Rap1 controls integrin alpha ( IIb ) beta3 activity and platelet aggregation ... Recently, we have found that Rap1 activation can be blocked by the nitric oxide/cyclic guanosine monophosphate ( NO/cGMP ) signaling pathway by type 1 cGMP dependent protein kinase (cGKI) ... Phosphorylation of Rap1GAP2 by cGKI might mediate inhibitory effects of NO/cGMP on Rap1
Mandell et al., J Biol Chem 2005 : Together, these results suggest that JAM1 regulates epithelial cell morphology and beta1 integrin expression by modulating activity of the small GTPase Rap1
Danielewski et al., Thromb Haemost 2005 (Calcium Signaling) : Four lines of evidence suggest that NO/cGMP effects are mediated by cGMP dependent protein kinase (cGKI) : ( i ) Rap 1 inhibition correlated with cGKI activity as measured by the phosphorylation state of VASP, an established substrate of cGKI, ( ii ) 8-pCPT-cGMP, a membrane permeable cGMP-analog and activator of cGKI, completely blocked Rap1 activation, ( iii ) Rp-8pCPT-cGMPS, a cGKI inhibitor, reversed NO effects and ( iv ) expression of cGKI in cGKI-deficient megakaryocytes inhibited Rap1 activation ... Thrombin-, ADP- and collagen induced formation of Rap 1-GTP in platelets as well as turbulence induced Rap 1 activation in megakaryocytes were inhibited ... Furthermore, cGKI inhibited ADP induced Rap 1 activation induced by the Galpha ( i ) -coupled P2Y12 receptor alone, i.e. independently of effects on Ca2+ signalling ... Furthermore, cGKI inhibited ADP induced Rap 1 activation induced by the Galpha ( i ) -coupled P2Y12 receptor alone, i.e. independently of effects on Ca2+ signalling ... From these studies we conclude that NO/cGMP inhibit Rap 1 activation in human platelets and that this effect is mediated by cGKI ... Since Rap1 controls the function of integrin alpha ( IIb ) beta3, we propose that Rap 1 inhibition might play a central role in the anti-aggregatory actions of NO/cGMP
Basoni et al., FASEB J 2005 : More importantly, TGF-beta1 greatly reduced the capacity of PMA or chemokines to activate CD11b and Rap1, a phenomenon paralleled by a loss of the Epac transcript and a reduction in 8-pCPT-2'-O-Me-cAMP mediated activation of Rap1 ... The inhibitory effect of TGF-beta1 on Rap1 activity may exert a general protective influence against aberrant transendothelial migration, thereby holding inflammatory responses in check
Huang et al., Oncogene 2005 : AKAP121 and G3BP expression was reduced, while dihydrofolate reductase (DHFR), Rap1 and RCC1 expression was elevated in response to PTEN expression in a PTEN-null T-cell leukemia line
Dillon et al., Mol Cell Biol 2005 : Regulation of the small GTPase Rap1 and extracellular signal regulated kinases by the costimulatory molecule CTLA-4 ... Together, CD3 and CTLA-4 activate Rap1 in a sustained manner ... We demonstrate that CTLA-4 activates Rap1 , and we propose that intracellular signals from CTLA-4 antagonize CD28, at least in part, at the level of Rap1
Regier et al., Proc Natl Acad Sci U S A 2005 (Neoplasms, Experimental) : Diacylglycerol kinase iota regulates Ras guanyl releasing protein 3 and inhibits Rap1 signaling ... Diacylglycerol kinase iota regulates Ras guanyl releasing protein 3 and inhibits Rap1 signaling ... Diacylglycerol kinase iota regulates Ras guanyl releasing protein 3 and inhibits Rap1 signaling ... In addition to activating Ras, RasGRP3 also activates Rap1 , which in some cases can antagonize the function of Ras ... In addition to activating Ras, RasGRP3 also activates Rap1 , which in some cases can antagonize the function of Ras ... We demonstrate that DGKiota bound to RasGRP3 and inhibited its activation of Rap1 by metabolizing DAG
Ji et al., Mol Cell Biol 2005 (Second Messenger Systems) : In NC cultures, high-level activation of cAMP signaling mediates protein kinase A (PKA) dependent Rap1-B-Raf-ERK1/2 activation, leading to cytoplasmic accumulation of phospho-Smad1, thus terminating bone morphogenetic protein 2 (BMP2) induced sympathoadrenal cell development
Moon et al., J Neurosci Res 2005 : Epac1 mediated Rap1 activation is not required for the production of nitric oxide in BV2, murine microglial cells ... In contrast, the Epac-specific cAMP analog 8- ( 4-chloro-phenylthio ) -2'-O-methyladenosine-3',5'-cyclic monophosphate ( 8CPT-2Me-cAMP ) activates Rap1 in the BV2 cells, but does not induce PKA activation, as judged by CREB phosphorylation ... This suggests that LPS stimulated NO production is mainly PKA dependent and also that Epac1 mediated Rap1 activation is not required for the induction of NO production
Fernández et al., J Mol Endocrinol 2005 : Studies in GH4C1 cells, with an expression vector for Rap1 GTPase activating protein ( Rap1 GAP1 ), demonstrated reduced VIP induced MAPK activation, indicating that VIP dependent activation of the extracellular signal regulated kinase ( ERK ) pathway requires PKA-Rap1 signaling
Kanemitsu et al., Blood 2005 : In vitro, CXCL13 activated the small guanosine triphosphatase ( GTPase ) Rap1 in B cells, and corroborating this observation, a deficiency of RAPL, the Rap1 effector molecule, caused a significant reduction in shear-resistant B-cell adhesion to intercellular adhesion molecule 1 ( ICAM-1 ) ... In vitro, CXCL13 activated the small guanosine triphosphatase ( GTPase ) Rap1 in B cells, and corroborating this observation, a deficiency of RAPL, the Rap1 effector molecule, caused a significant reduction in shear-resistant B-cell adhesion to intercellular adhesion molecule 1 ( ICAM-1 )
Cho et al., Biochem Biophys Res Commun 2005 (Leukemia) : Moreover, the presence of Rap1 further promoted tyrosine phosphorylation of C3G and Cas
Li et al., Blood 2005 : T-cell receptor (TCR)-CD3/CD28 mediated activation of Rap1 and Akt was retained in Tregs, but activation of Ras, mitogenactivated protein kinase 1/2 ( MEK1/2 ), and extracellular signal regulated kinase 1/2 ( Erk1/2 ) was impaired ... T-cell receptor (TCR)-CD3/CD28 mediated activation of Rap1 and Akt was retained in Tregs, but activation of Ras, mitogenactivated protein kinase 1/2 ( MEK1/2 ), and extracellular signal regulated kinase 1/2 ( Erk1/2 ) was impaired ... T-cell receptor (TCR)-CD3/CD28 mediated activation of Rap1 and Akt was retained in Tregs, but activation of Ras, mitogenactivated protein kinase 1/2 ( MEK1/2 ), and extracellular signal regulated kinase 1/2 ( Erk1/2 ) was impaired ... T-cell receptor (TCR)-CD3/CD28 mediated activation of Rap1 and Akt was retained in Tregs, but activation of Ras, mitogenactivated protein kinase 1/2 ( MEK1/2 ), and extracellular signal regulated kinase 1/2 ( Erk1/2 ) was impaired
Han et al., J Exp Med 2005 (Calcium Signaling...) : Both compounds blocked TNF induced activation of Rap1A , a phox associated guanosine triphosphatase that is regulated by cAMP
Stork et al., Blood 2005 : Rap1 may also regulate cellular differentiation and proliferation via pathways that are distinct from those mediating adhesion, and involve regulation of the mitogen activated protein ( MAP ) kinase or ERK ( extracellular signal regulated kinase ) cascade
Schneider et al., Proc Natl Acad Sci U S A 2005 (Tissue Adhesions) : CTLA-4 up-regulated adhesion was mediated by regulator for cell adhesion and polarization type 1 ( Rap-1 ) as shown by anti-CTLA-4 induced Rap-1 activation as well as Rap-1-N17 blockade and Rap-1-V12 mimicry of adhesion/clustering
Sato et al., Cancer Sci 2005 : The activation of Cdc42 and Rac by the trans-interaction of nectin and nectin is mediated by c-Src, another small G protein, Rap1 , a Cdc42-GEF, FRG, and a Rac-GEF, Vav2 ... The activation of Cdc42 and Rac by the trans-interaction of nectin and nectin is mediated by c-Src, another small G protein, Rap1 , a Cdc42-GEF, FRG, and a Rac-GEF, Vav2 ... The trans-interaction of Necl-5 and nectin-3 also activates Rap1 through C3G, a Rap-GEF, and this activation of Rap1 is required for the activation of Cdc42 and Rac ... The trans-interaction of Necl-5 and nectin-3 also activates Rap1 through C3G, a Rap-GEF, and this activation of Rap1 is required for the activation of Cdc42 and Rac
Fukuyama et al., Oncogene 2006 : The c-Src catalysed tyrosine phosphorylation was not sufficient for the activation of Vav2 and the c-Src induced activation of Rap1 was additionally necessary for it, although activated Rap1 alone was not sufficient for the activation of non-tyrosine phosphorylated Vav2 ... The c-Src catalysed tyrosine phosphorylation was not sufficient for the activation of Vav2 and the c-Src induced activation of Rap1 was additionally necessary for it, although activated Rap1 alone was not sufficient for the activation of non-tyrosine phosphorylated Vav2 ... This effect of Rap1 on Vav2 was mediated by phosphatidylinositol 3-kinase
Jenei et al., Exp Cell Res 2005 : E3B1, a human homologue of the mouse gene product Abi-1, sensitizes activation of Rap1 in response to epidermal growth factor ... Remarkably, we found that EGF induced activation of the p21Ras related GTPase Rap1 was also sensitized in NIH3T3/EGFR-e3B1 cells ... Thus, in NIH3T3/EGFR-e3B1 cells, maximal EGF induced activation of Rap1 occurs with a dose of EGF much lower than in NIH3T3/EGFR cells ... We also report that overexpression of e3B1 in NIH3T3/EGFR cells renders EGF induced activation of Rap1 completely dependent on Src tyrosine kinases but not on c-Abl ... Accordingly, we propose that overexpression of e3B1 in NIH3T3/EGFR cells leads to mobilization of Src tyrosine kinases that participate in EGF induced activation of Rap1 and inhibition of cell proliferation
Balzac et al., J Cell Sci 2005 : Here, we demonstrate that the small GTPase Rap1 , a crucial regulator of the inside-out activation of integrins, is a target for E-cadherin mediated outside-in signaling ... Furthermore, we demonstrate that the E-cadherin endocytosis dependent activation of Rap1 is associated with and controlled by an increased Src kinase activity, and is paralleled by the colocalization of Rap1 and E-cadherin at the perinuclear Rab11 positive recycling endosome compartment, and the association of Rap1 with a subset of E-cadherin-catenin complexes that does not contain p120ctn ... Finally, we demonstrate that the E-cadherin endocytosis dependent activation of Rap1 is associated with and is required for the formation of integrin based focal adhesions
Hokari et al., Am J Physiol Gastrointest Liver Physiol 2005 : cAMP/Epac/Rap1/B-Raf signaling was not involved in MUC2 reporter activation
Sakurai et al., Mol Biol Cell 2006 : MAGI-1 is required for Rap1 activation upon cell-cell contact and for enhancement of vascular endothelial cadherin mediated cell adhesion ... We demonstrate for the first time that Rap1 is activated upon homophilic engagement of vascular endothelial cadherin ( VE-cadherin ) at the cell-cell contacts in living cells and that MAGI-1 is required for VE-cadherin dependent Rap1 activation ... We demonstrate for the first time that Rap1 is activated upon homophilic engagement of vascular endothelial cadherin ( VE-cadherin ) at the cell-cell contacts in living cells and that MAGI-1 is required for VE-cadherin dependent Rap1 activation ... We demonstrate for the first time that Rap1 is activated upon homophilic engagement of vascular endothelial cadherin ( VE-cadherin ) at the cell-cell contacts in living cells and that MAGI-1 is required for VE-cadherin dependent Rap1 activation ... Collectively, MAGI-1 is important for VE-cadherin dependent Rap1 activation upon cell-cell contact
Jung et al., Thromb Res 2006 : Analyzing the mechanism of Rap1 activation in platelets : Rap1 activation is related to the release reaction mediated through the collagen receptor GPVI
Catalano et al., Blood 2006 (MAP Kinase Signaling System...) : The presence of Sema-3A increased the activation of the Ras family small GTPase Rap1 and introduction of the dominant negative mutant of Rap1 ( Rap1N17 ) blunted the immunoinhibitory effects of Sema-3A
Calipel et al., J Biol Chem 2006 (Cell Transformation, Neoplastic...) : This ruled out a role for Rap1 in the PKA mediated B-Raf/ERK activation in ( WT ) B-Raf cells ... This ruled out a role for Rap1 in the PKA mediated B-Raf/ERK activation in ( WT ) B-Raf cells
Oh et al., Oncogene 2006 : Therefore, TIMP-2 mediated inhibition of Src kinase activity leads to the signaling switch from Rac1 to Rap1 , thereby leading to enhanced RECK expression
Wang et al., Mol Cell Biol 2006 : We confirm that the PKA independent activation of Rap1 by Epac1 activates a perinuclear pool of Rap1 and that this does not result in ERK activation ... We confirm that the PKA independent activation of Rap1 by Epac1 activates a perinuclear pool of Rap1 and that this does not result in ERK activation ... Rap1 activation by Epac-CAAX, but not wild-type Epac, triggers its association with B-Raf ... Using a small interfering RNA approach, we demonstrate that C3G is required for the activation of ERKs and Rap1 by cAMP/PKA
Retta et al., Eur J Cell Biol 2006 : This review focuses on recent findings on the involvement of the small GTPase Rap1 in the regulation of cadherin- and integrin dependent cell adhesion and signal transduction
Stessin et al., J Biol Chem 2006 : Soluble adenylyl cyclase mediates nerve growth factor induced activation of Rap1 ... These inhibitors, along with sAC-specific small interfering RNA, reveal that sAC is uniquely responsible for the NGF elicited rise in cAMP and is essential for the NGF induced activation of the small G protein Rap1 in PC12 cells ... These inhibitors, along with sAC-specific small interfering RNA, reveal that sAC is uniquely responsible for the NGF elicited rise in cAMP and is essential for the NGF induced activation of the small G protein Rap1 in PC12 cells ... In contrast and as expected, transmembrane adenylyl cyclase generated cAMP is responsible for Rap1 activation by the G protein coupled receptor ligand PACAP ( pituitary adenylyl cyclase activating peptide )
Sakamoto et al., J Biol Chem 2006 : An immunoglobulin-like cell-cell adhesion molecule nectin first trans-interacts with each other to form cell-cell adhesion and induces activation of Rap1 , Cdc42, and Rac small G proteins through c-Src ... An immunoglobulin-like cell-cell adhesion molecule nectin first trans-interacts with each other to form cell-cell adhesion and induces activation of Rap1 , Cdc42, and Rac small G proteins through c-Src
Chang et al., Biochem Biophys Res Commun 2006 : Here, we show that TIMP-2 overexpression in hMVECs by adenoviral infection enhances Rap1 expression, leading to further increase in Rap1-GTP ... TIMP-2 greatly promotes the association of Rap1 with actin
Beaudry et al., Endocrinology 2006 : Treatment of cells with Gö6976 was also found to inhibit p21(ras) ( between 1-10 min ) but stimulated Rap1 activity ( 1-5 min ) in a time-course similar to that of Ang II
Bryn et al., J Immunol 2006 : In this study, we demonstrate the presence of Epac1 in human peripheral blood monocytes and activation of Rap1 in response to cAMP
Lafuente et al., Methods Enzymol 2006 : Rap1 regulation of RIAM and cell adhesion ... Finally, we describe an approach to determine the role of RIAM in regulating intracellular localization of active Rap1
Uchida et al., J Cell Sci 2006 : We also found that Dok-4 induced a significant activation of the small G protein Rap1 and that expression of a dominant active Rap1 mutant restored neurite outgrowth in Dok-4 depleted cells ... We also found that Dok-4 induced a significant activation of the small G protein Rap1 and that expression of a dominant active Rap1 mutant restored neurite outgrowth in Dok-4 depleted cells
Holinstat et al., J Biol Chem 2006 (Calcium Signaling) : Furthermore, we show that P2Y12 receptor activation is not required for protease activated receptor mediated aggregation at higher agonist concentrations and is only partially required for Rap1 as well as GPIIbIIIa activation
Romano et al., Endocrinology 2006 : Under the same conditions, PI3K and Akt inhibition also both increased Raf-1 kinase activity and the levels of GTP bound ( active form ) monomeric G protein Rap1 , which suggests that a down-regulation of the ERK-1/2 cascade is induced by the PI3K/Akt signaling pathway in unstimulated cells ... Under the same conditions, PI3K and Akt inhibition also both increased Raf-1 kinase activity and the levels of GTP bound ( active form ) monomeric G protein Rap1 , which suggests that a down-regulation of the ERK-1/2 cascade is induced by the PI3K/Akt signaling pathway in unstimulated cells ... Under the same conditions, PI3K and Akt inhibition also both increased Raf-1 kinase activity and the levels of GTP bound ( active form ) monomeric G protein Rap1 , which suggests that a down-regulation of the ERK-1/2 cascade is induced by the PI3K/Akt signaling pathway in unstimulated cells
Jenei et al., J Biol Chem 2006 (Calcium Signaling) : Also, the activation of Rap1 was blocked by PP1 , SU6656, LY294002, GF109203X, or BAPTA-AM, which indicates that the downstream signaling events in Rap1 activation involve Src tyrosine kinases, phosphoinositide 3-kinase, protein kinase C, and release of calcium
He et al., Can J Physiol Pharmacol 2006 : The CB1 cannabinoid receptor , a Go/i coupled receptor expressed endogenously in Neuro2A cells, triggers neurite outgrowth by activating Rap1 , which promotes the Galphao stimulated proteasomal degradation of Rap1GAPII ... CB1-receptor mediated Rap1 activation leads to the activation of a signaling network that includes the small guanosine triphosphate ( GTP ) ases Ral and Rac, the protein kinases Src, and c-Jun N-terminal kinase (JNK), which converge onto the activation of signal transducer and activator of transcription 3 ( Stat3 ), a key transcription factor that mediates the gene expression process of neurite outgrowth in Neuro2A cells
Wang et al., J Biol Chem 2006 : Here, we report that BDNF induces a sustained activation of ERK5 in rat cortical neurons and activates Rap1 , a small GTPase, as well as MEKK2, a MEK5 kinase ... Our data indicate that activation of Rap1 or MEKK2 is sufficient to stimulate ERK5, whereas inhibition of either Rap1 or MEKK2 attenuates BDNF activation of ERK5 ... Our data indicate that activation of Rap1 or MEKK2 is sufficient to stimulate ERK5, whereas inhibition of either Rap1 or MEKK2 attenuates BDNF activation of ERK5 ... Furthermore, BDNF stimulation of MEKK2 is regulated by Rap1 ... Furthermore, BDNF stimulation of MEKK2 is regulated by Rap1
Kogut et al., Mol Immunol 2007 : Using a Rap1-GTP pull-down assay, we found that FLG stimulation, but not LPS, of avian heterophils induced a rapid and transient Rap1 activation ... Using a Rap1-GTP pull-down assay, we found that FLG stimulation, but not LPS , of avian heterophils induced a rapid and transient Rap1 activation ... Rap1 has been shown to activate the ERK1/2 via a different Raf family member B-Raf whose downstream effector is MEK1/2 ... We show here that FLG stimulation of heterophils induces the phosphorylation of Rap1
Li et al., Mol Endocrinol 2007 (Colorectal Neoplasms) : The small GTPase Rap1 can be activated by both PKA and Epac ; however, the role of Rap1 in hormone secretion is unknown ... PKA activation increased NT release and Rap1 activity
Sawada et al., Cell 2006 (Mechanotransduction, Cellular) : Previously, we showed that tyrosine phosphorylation of p130Cas ( Cas ) in a cytoskeletal complex is involved in force dependent activation of the small GTPase Rap1 ... Previously, we showed that tyrosine phosphorylation of p130Cas ( Cas ) in a cytoskeletal complex is involved in force dependent activation of the small GTPase Rap1
De Falco et al., Cancer Res 2007 (Carcinoma, Papillary...) : Here, we show that RET/PTC1 activates the Rap1 small GTPase ... Here, we show that RET/PTC1 activates the Rap1 small GTPase ... The activation of Rap1 was dependent on the phosphorylation of RET Tyr ( 1062 ) ... By using dominant negative and small interfering duplex ( small interfering RNA ) oligonucleotides, we show that RET/PTC1 mediated Rap1 activation was dependent on CrkII, C3G, and Gab1 ... By using dominant negative and small interfering duplex ( small interfering RNA ) oligonucleotides, we show that RET/PTC1 mediated Rap1 activation was dependent on CrkII, C3G, and Gab1 ... By using dominant negative and small interfering duplex ( small interfering RNA ) oligonucleotides, we show that RET/PTC1 mediated Rap1 activation was dependent on CrkII, C3G, and Gab1 ... Activation of Rap1 was involved in the RET/PTC1 mediated stimulation of the BRAF kinase and the p42/p44 mitogen activated protein kinases ... Activation of Rap1 was involved in the RET/PTC1 mediated stimulation of the BRAF kinase and the p42/p44 mitogen activated protein kinases
Obara et al., J Neurochem 2007 : We show that both Ras and Rap1 can be activated by cAMP or PACAP via protein kinase (PKA) dependent mechanisms ... We show that both Ras and Rap1 can be activated by cAMP or PACAP via protein kinase (PKA) dependent mechanisms
Karhoff et al., Neuroendocrinology 2007 (Digestive System Neoplasms...) : In endocrine cells, the small G-protein Rap1 stimulates mitogen activated protein kinase ( MAPK ) signaling by activating B-Raf ... Overexpression of Rap1 and B-Raf activated MAPK extracellular dependent kinase (ERK) ERK-2 and ERK dependent transcription factor Elk-1 in neuroendocrine cell lines Bon and INS-1 ... Overexpression of Rap1 and B-Raf activated MAPK extracellular dependent kinase (ERK) ERK-2 and ERK dependent transcription factor Elk-1 in neuroendocrine cell lines Bon and INS-1
Gérard et al., J Cell Biol 2007 : Intracellular localization and activation of the Par complex are initiated by Rap1 and require Cdc42 activity
Minato et al., Adv Immunol 2007 (Neoplasms) : Rap1 also regulates MAP kinase ( MAPK ) activity in a manner highly dependent on the context of cell types
Xie et al., Mol Pharmacol 2007 (MAP Kinase Signaling System...) : Furthermore, PKA dependent Rap1 activation is required for both ERK1/2 activation and androgen independent AR activation in LNCaP cells upon VIP stimulation ... Furthermore, PKA dependent Rap1 activation is required for both ERK1/2 activation and androgen independent AR activation in LNCaP cells upon VIP stimulation
Wakamatsu et al., J Biol Chem 2007 : Moreover, Ca2+ induced activation of ERK through Rap1 and expression of loricrin were reduced in primary cultured nectin-1-/- keratinocytes ; in turn, the inhibition of ERK activation reduced the amount of loricrin in wild-type keratinocytes
Birukova et al., Exp Cell Res 2007 (Respiratory Distress Syndrome, Adult) : Prostaglandins PGE ( 2 ) and PGI ( 2 ) promote endothelial barrier enhancement via PKA- and Epac1/Rap1 dependent Rac activation
Parmo-Cabañas et al., J Leukoc Biol 2007 : CCL25 rapidly activated the GTPases Rac and Rap1 on thymocytes, and this activation was required for stimulation of adhesion, as detected using the CCR9 ( + ) /alpha4beta1 ( + ) human T cell line Molt-4
Jeong et al., J Biol Chem 2007 : Overexpression of IQGAP1 substantially reduces adhesion mediated activation of Rap1
Moon et al., Immunol Lett 2007 : Here, we investigated whether NF-kappaB can be activated by cAMP production through Epac1 mediated Rap1 activation by using Epac-specific cAMP analogue, 8- ( 4-chloro-phenylthio ) -2'-O-methyladenosine-3',5'-cyclic monophosphate ( CPT ) ... In conclusion, NF-kappaB activation should be regulated through Epac1 mediated Rap1 stimulation for LPS induced inflammatory responses in murine macrophages
Yoshikawa et al., Mol Biol Cell 2007 : Here, we show that RA-GEF-2 is specifically responsible for the activation of Rap1 that mediates tumor necrosis factor-alpha (TNF-alpha) triggered integrin activation ... Here, we show that RA-GEF-2 is specifically responsible for the activation of Rap1 that mediates tumor necrosis factor-alpha (TNF-alpha) triggered integrin activation ... TNF-alpha treatment activated LFA-1 in a manner dependent on M-Ras, RA-GEF-2, and Rap1 and induced activation of M-Ras and Rap1 in the plasma membrane, which was accompanied by recruitment of RA-GEF-2
Glodek et al., Leukemia 2007 (Precursor B-Cell Lymphoblastic Leukemia-Lymphoma) : FAK-deficient REH cells also demonstrated reduced CXCL12 induced activation of the GTPase Rap1 , suggesting the importance of FAK in CXCL12 mediated integrin activation
Dremier et al., Endocrinology 2007 : The TSH induced activation of Rap1 was presumably mediated by Epac1 because it was mimicked by the Epac-selective cAMP analog ( 8-p-chloro-phenyl-thio-2'-O-methyl-cAMP ) and not by PKA-selective cAMP analogs
Merrell et al., Eur J Pharmacol 2007 (Breast Neoplasms) : Also mevastatin induced the accumulation of unprenylated Rap1A , but it did not induce p38 phosphorylation
Hisata et al., J Cell Biol 2007 : PDZ-GEF1 is activated by GTP-Rap1 via a positive feedback mechanism ... Thus, the interaction of PDZ-GEF1 with an internalized neurotrophin receptor transported to late endosomes induces sustained activation of both Rap1 and ERK and neurite outgrowth
Potapova et al., FEBS J 2007 (Ion Channel Gating) : In contrast, activation of Rap-1 was affected dramatically by coexpression of Kv4.3 and Kv channel interacting protein 2 with the angiotensin type 1 receptor
Wu et al., Traffic 2007 (MAP Kinase Signaling System) : Moreover, NGF induced activation of Rap1 and sustained activation of MAPK1/2 were markedly suppressed ... Moreover, NGF induced activation of Rap1 and sustained activation of MAPK1/2 were markedly suppressed
Vachon et al., Blood 2007 : Taken together, these data suggest that CD44 stimulation induces inside-out activation of CR3 through the GTPase Rap1
Béraud-Dufour et al., FEBS J 2007 : Krit 1 interactions with microtubules and membranes are regulated by Rap1 and integrin cytoplasmic domain associated protein-1 ... Using sedimentation assays, we show that Krit1 binds in vitro to microtubules through its N- and C-termini and that Rap1 and ICAP-1 inhibit Krit1 binding to microtubules
Glading et al., J Cell Biol 2007 : Rap1 activity regulated the junctional localization of KRIT-1 and its physical association with junction proteins
Brock et al., Exp Cell Res 2008 : The absence of Rap1 on late phagosomes suggests that the effect of Epac-1 might not require Rap1
Shibasaki et al., Proc Natl Acad Sci U S A 2007 : In addition, the small GTPase Rap1 , which is activated by cAMP specifically through Epac2 in pancreatic beta cells, mediates cAMP induced insulin secretion in a protein kinase A-independent manner
Taniguchi et al., Cell Death Differ 2008 : Here, we report that soluble MAG induces activation of Rap1 in postnatal cerebellar granule neurons ( CGNs ) and dorsal root ganglion ( DRG ) neurons
Hochbaum et al., J Biol Chem 2008 : Since cAMP mediated activation of the G-protein Rap1 and its phosphorylation by PKA are strictly required for the effects of cAMP on mitogenesis, we hypothesized that the Rap1 activator Epac might represent the PKA independent factor
Ikuta et al., Cancer Res 2008 (Dermatitis, Contact...) : Experiments using small interfering RNA mediated knockdown indicate that this activation is mediated by Rap1 , which is activated by a TPA-responsive guanine nucleotide exchange factor RasGRP3
Wang et al., Blood 2008 (Leukemia-Lymphoma, Adult T-Cell) : The results suggested that deregulated constitutive Rap1 activation caused abnormal expansion of DP thymocytes, bypassing the pre-T-cell receptor and eventually leading to Notch1 mutations and Notch dependent T-ALL
Bendjennat et al., J Biol Chem 2008 : TBP-Rap1p complex formation inhibits TBP binding to TATA promoter DNA
Maruta et al., J Biol Chem 1991 : In this paper, we describe the enzymatic properties of several mutated Rap1A and chimeric Ras/Rap1A ( or -1B ) proteins which lead to the following conclusions : ( i ) the GAP3 dependent activation of both Rap1A and -1B GTPases requires Gly12, but neither Thr61 nor Gln63 ; ( ii ) residues 64 to 70 of the Rap1 GTPases are sufficient to determine their specificities for GAP3 ; and ( iii ) residues 61 to 65 of the Ras GTPases are sufficient for determining their specificities for GAP1
Chen et al., Blood 2008 : Furthermore, we found that Rap1b deficiency had no marked effect on LPS-, BCR-, or SDF-1 induced activation of mitogen activated protein kinases and AKT but clearly impaired SDF-1 mediated activation of Pyk-2 , a key regulator of SDF-1 mediated B-cell migration
Ravni et al., Mol Pharmacol 2008 : PACAP signaling to neuritogenesis was also impaired by dominant negative Rap1 expression but was not affected by inhibition of protein kinase C ( PKC ), indicating a G-protein coupled receptor mediated differentiation pathway distinct from the one activated by receptor tyrosine kinase ligands such as nerve growth factor (NGF), that involves both Rap1 and PKC ... PACAP signaling to neuritogenesis was also impaired by dominant negative Rap1 expression but was not affected by inhibition of protein kinase C ( PKC ), indicating a G-protein coupled receptor mediated differentiation pathway distinct from the one activated by receptor tyrosine kinase ligands such as nerve growth factor (NGF) , that involves both Rap1 and PKC ... Dominant negative Rap1 expression impairs both PACAP induced neuritogenesis and Egr1 activation by PACAP, suggesting that cAMP elevation and ERK activation by PACAP are linked through Rap1
Banno et al., Biochem Soc Trans 2008 : Rap1 activation caused the formation of an ` activation complex ' containing talin and RIAM that redistributed to the plasma membrane and activated alphaIIbbeta3
Mitra et al., Cancer Res 2008 (Carcinoma, Squamous Cell...) : Rap1GAP up-regulated transcription and secretion of MMP2 and MMP9, as assayed by quantitative reverse transcription-PCR and zymography ... Rap1GAP up-regulated transcription and secretion of MMP2 and MMP9 , as assayed by quantitative reverse transcription-PCR and zymography
Cifuni et al., Blood 2008 : Independent roles for CalDAG-GEFI and PKC/Galphai signaling were also observed for PAR4p induced activation of the small GTPase Rap1 , with CalDAG-GEFI mediating the rapid but reversible activation of this small GTPase
Dubé et al., Cell Signal 2008 : Since junctions in Rap1B depleted cells have a mature appearance, these data suggest that PDZ-GEF2 activates Rap1A and Rap1B to perform different functions
Yokoyama et al., J Biol Chem 2008 : A specific EP4 agonist, ONO-AE1-329, increased Rap1 activity in the presence of a PKA inhibitor, PKI- ( 14-22 ) -amide, in DA smooth muscle cells
Lastres-Becker et al., Mol Cell Neurosci 2008 : PACAP also activates the small GTPases Rap1 and Ras, but either activation of Rap1 alone by selective stimulation of the guanine nucleotide exchange factor Epac, or expression of a constitutively active form of Ras, do not induce GFAP gene expression ... PACAP also activates the small GTPases Rap1 and Ras, but either activation of Rap1 alone by selective stimulation of the guanine nucleotide exchange factor Epac, or expression of a constitutively active form of Ras, do not induce GFAP gene expression ... Thus, cAMP dependent PACAP induced GFAP expression during astrocytogenesis involves the coordinated activation of both Ras and Rap1 , but activation of either one of them in isolation is not sufficient to trigger this response
Letschka et al., Blood 2008 : After T-cell activation, the direct phosphorylation of RapGEF2 at Ser960 by PKC- theta regulates Rap1 activation as well as LFA-1 adhesiveness to ICAM-1
Arora et al., Mol Biol Cell 2008 : Rap1 activation in collagen phagocytosis is dependent on nonmuscle myosin II-A
Nolz et al., J Cell Biol 2008 : The WAVE2 complex regulates T cell receptor signaling to integrins via Abl- and CrkL-C3G mediated activation of Rap1
Li et al., J Biol Chem 2008 : Inhibition of PI3K or mTOR reduced the level of Rap1B , which acts downstream of Rheb and mTOR ... Inhibition of PI3K or mTOR reduced the level of Rap1B , which acts downstream of Rheb and mTOR
Aivatiadou et al., Mol Reprod Dev 2009 : cAMP-Epac2 mediated activation of Rap1 in developing male germ cells : RA-RhoGAP as a possible direct down-stream effector
Oestreich et al., J Biol Chem 2009 (Calcium Signaling) : Here we demonstrate that PLCepsilon phosphatidylinositol 4,5-bisphosphate hydrolytic activity and PLCepsilon stimulated Rap1 GEF activity are both required for PLCepsilon mediated enhancement of sarcoplasmic reticulum Ca2+ release and that PLCepsilon significantly enhances Rap activation in response to betaAR stimulation in the heart
Zhang et al., Cell Signal 2009 (MAP Kinase Signaling System) : Here, we show that PACAP recruits Rap1 into caveolin enriched membrane subdomains in PC12 cells and activates Rap1 , nuclear ERK1/2, Elk-1 and CREB in a caveolae dependent manner
Nellore et al., J Clin Endocrinol Metab 2009 (Carcinoma, Papillary...) : Rap1 GTPase activating protein (GAP) regulates the activity of Rap1 , a putative oncogene ... Rap1 GTPase activating protein (GAP) regulates the activity of Rap1 , a putative oncogene ... In vitro, loss of Rap1GAP was sufficient to increase Rap1 activity in thyroid cells ... In vitro, loss of Rap1GAP was sufficient to increase Rap1 activity in thyroid cells
Rufanova et al., J Cell Physiol 2009 : Downregulation of endogenous BCAR3 protein expression using an siRNA technique led to a significant decrease in Rap1 activation in response to ET-1
Zheng et al., Cancer Res 2009 (Melanoma) : In the present study, we show that expression of Rap1GAP , a specific negative regulator of Rap1 , is decreased in human melanoma tumors and cell lines ... In the present study, we show that expression of Rap1GAP , a specific negative regulator of Rap1 , is decreased in human melanoma tumors and cell lines ... Overexpression of Rap1GAP in melanoma cells blocks Rap1 activation and extracellular signal regulated kinase ( ERK ) phosphorylation and inhibits melanoma cell proliferation and survival ... Overexpression of Rap1GAP in melanoma cells blocks Rap1 activation and extracellular signal regulated kinase ( ERK ) phosphorylation and inhibits melanoma cell proliferation and survival
McAvoy et al., Proc Natl Acad Sci U S A 2009 : We have identified a prominent striatal PKA substrate as Rap1-GTPase activating protein (Rap1GAP) , a negative regulator of Rap1 signaling
Mor et al., Mol Cell Biol 2009 : Moreover, PLD activity is required for both translocation and activation of Rap1 ... Our data support a model whereby PLD1 regulates Rap1 activity by controlling exocytosis of a stored, vesicular pool of Rap1 that can be activated by C3G upon delivery to the plasma membrane
Guidetti et al., Journal of thrombosis and haemostasis : JTH 2009 : Platelet adhesion promoted by integrin alpha2beta1 induces integrin alpha ( IIb ) beta3 activation through the phospholipase C (PLC) dependent stimulation of the small GTPase Rap1b ... Importantly, alpha ( IIb ) beta3 induced phosphorylation and activation of PLCgamma2, as well as accumulation of active Rap1b , were totally suppressed by Src inhibition ... However, when phosphorylation of PLCgamma2 was blocked by the Src kinase inhibitor PP2, prevention of Rac1 activation significantly reduced PLCgamma2 activation, GTP-Rap1b accumulation, and alpha ( IIb ) beta3 stimulation
Segovis et al., J Immunol 2009 : Furthermore, our data indicate that the small Ras family GTPase Rap1 is activated downstream of NKG2D engagement in a PI3K- and CrkL dependent manner and is required for conjugate formation, MTOC ( microtubule organizing center ) polarization, and NKG2D dependent cellular cytotoxicity
Bailey et al., Cancer Res 2009 (Neoplasm Invasiveness...) : Additional studies implicate integrins alpha4, beta3, and alphavbeta3 in the mechanism of Rap1 mediated CaP migration and invasion
Gérard et al., J Immunol 2009 : Exogenous expression of wild-type Dok-4 induces a significant activation of Rap1 , which is involved in the regulation of ERK
Schubert et al., Transfusion 2009 : A signaling pathway contributing to platelet storage lesion development : targeting PI3-kinase dependent Rap1 activation slows storage induced platelet deterioration ... These results provide the first evidence for a signaling pathway mediating PSL in which PI3-kinase dependent Rap1 activation leads to integrin alphaIIbbeta3 activation and PLT degranulation
Canobbio et al., Blood 2009 : However, PI3Kbeta, but not PI3Kgamma, enzymatic activity was absolutely required for Akt phosphorylation, Rap1 activation , and platelet aggregation downstream of the immunoreceptor tyrosine based activation motif ( ITAM ) -bearing receptor glycoprotein VI (GPVI) ... However, PI3Kbeta , but not PI3Kgamma, enzymatic activity was absolutely required for Akt phosphorylation, Rap1 activation, and platelet aggregation downstream of the immunoreceptor tyrosine based activation motif ( ITAM ) -bearing receptor glycoprotein VI (GPVI) ... However, PI3Kbeta, but not PI3Kgamma , enzymatic activity was absolutely required for Akt phosphorylation, Rap1 activation, and platelet aggregation downstream of the immunoreceptor tyrosine based activation motif ( ITAM ) -bearing receptor glycoprotein VI (GPVI)
Kanemura et al., Biochem Biophys Res Commun 2009 : Reduced accumulation of VE-cadherin at cell-cell junctions and defects in blood vessel formation in vitro due to the lack of RA-GEF-1 were suppressed by ectopic expression of constitutively activated Rap1
Edreira et al., J Biol Chem 2009 : cAMP dependent protein kinase (PKA) mediated phosphorylation of Rap1b is required for cAMP dependent mitogenesis, tumorigenesis, and inhibition of AKT activity
Gilio et al., J Biol Chem 2009 (Thrombosis) : Furthermore, PI3Kalpha/beta, but not PI3Kgamma, contributed to GPVI induced Rap1b activation and, surprisingly, also to Rap1b independent platelet activation via GPVI ... Furthermore, PI3Kalpha/beta , but not PI3Kgamma, contributed to GPVI induced Rap1b activation and, surprisingly, also to Rap1b independent platelet activation via GPVI ... Furthermore, PI3Kalpha/beta , but not PI3Kgamma, contributed to GPVI induced Rap1b activation and, surprisingly, also to Rap1b independent platelet activation via GPVI ... Furthermore, PI3Kalpha/beta, but not PI3Kgamma , contributed to GPVI induced Rap1b activation and, surprisingly, also to Rap1b independent platelet activation via GPVI
Malchinkhuu et al., Mol Biol Cell 2009 (Glioma) : The expression of tumor suppressor phosphatase and tensin homolog deleted on chromosome 10 ( PTEN ) is required for the inhibitory ISO induced and Rap1B mediated actions on the migration, Rac1 activation, and Akt activation in response to LPA ... The expression of tumor suppressor phosphatase and tensin homolog deleted on chromosome 10 ( PTEN ) is required for the inhibitory ISO induced and Rap1B mediated actions on the migration, Rac1 activation, and Akt activation in response to LPA ... Thus, the PTEN mediated down-regulation of phosphatidylinositol 3-kinase activity may be involved in the regulation of Rap1B dependent inhibition of Rac1 activity
He et al., Am J Physiol Heart Circ Physiol 2010 : PKA, Rap1 , ERK1/2, and p90RSK mediate PGE2 and EP4 signaling in neonatal ventricular myocytes
Kudo et al., Mediators Inflamm 2009 : Cathepsin G promotes E-cadherin/catenin complex formation and Rap1 activation in MCF-7 cells, which reportedly regulates E-cadherin based cell-cell junctions
Goto et al., Clin Cancer Res 2010 (Carcinoma, Squamous Cell...) : Rap1 stabilizes beta-catenin and enhances beta-catenin dependent transcription and invasion in squamous cell carcinoma of the head and neck ... Prior findings suggested that Rap1 may modulate the beta-catenin independent Wnt pathway in some settings, but the role of Rap1 in beta-catenin dependent Wnt signaling remains undefined ... Immunofluorescence studies showed that ectopic expression of Rap1 increased nuclear translocation of beta-catenin ... The findings suggest that Rap1 enhances beta-catenin stability and nuclear localization
Ahmed et al., J Biol Chem 2010 : Moreover, we demonstrate that Gbetagamma and activated Rap1a promote the translocation of Radil to the plasma membrane at sites of cell-matrix contacts
Zuo et al., Cancer Res 2010 (Carcinoma, Papillary, Follicular...) : Rap1GAP , a Rap1 GTPase activating protein, inhibits the RAS superfamily protein Rap1 by facilitating hydrolysis of GTP to GDP ... Rap1GAP , a Rap1 GTPase activating protein, inhibits the RAS superfamily protein Rap1 by facilitating hydrolysis of GTP to GDP
Schönherr et al., Oncogene 2010 (Cell Transformation, Neoplastic...) : Anaplastic lymphoma kinase activates the small GTPase Rap1 via the Rap1-specific GEF C3G in both neuroblastoma and PC12 cells ... These results suggest that ALK activation of Rap1 may contribute to cell proliferation and oncogenesis of neuroblastoma driven by gain-of-function mutant ALK receptors
Jeon et al., Exp Mol Med 2010 : Contrary to RhoA, Rap1 was activated by NGF , and DN-Rap1 suppressed neurite outgrowth, suggesting that Rap1 is also essential for neurite outgrowth ... These results suggest that NGF activates Rap1 , which, in turn, up-regulates ARAP3 leading to RhoA inactivation and neurite outgrowth from PC12 cells
Kelly et al., J Biol Chem 2010 (Diabetes Mellitus) : Using the Ins-1 rat insulinoma line, we demonstrate that activated Rap1A , but not related monomeric G proteins, promotes ribosomal protein S6 phosphorylation ... Activated Rap1A promotes glucose stimulated insulin secretion, islet cell hypertrophy, and islet cell proliferation, the latter exclusively through mammalian target of rapamycin complex 1, suggesting that Rap1 is an important regulator of beta-cell function
Carbo et al., J Leukoc Biol 2010 : Interestingly, Rap1b-/- neutrophils had a similar phenotype in this assay, suggesting that CalDAG-GEFI may be acting through Rap1b
Tawa et al., Circ Res 2010 (Disease Models, Animal...) : These results demonstrate a novel molecular mechanism by which Rap1 and afadin regulate the VEGF- and S1P induced angiogenesis ... Rap1 regulated the interaction between afadin and phosphatidylinositol 3-kinase (PI3K), recruitment of the afadin-PI3K complex to the leading edge, and the activation of Akt , indicating the involvement of Rap1 and afadin in the PI3K-Akt signaling pathway ... Rap1 regulated the interaction between afadin and phosphatidylinositol 3-kinase (PI3K) , recruitment of the afadin-PI3K complex to the leading edge, and the activation of Akt, indicating the involvement of Rap1 and afadin in the PI3K-Akt signaling pathway
Guimond et al., Mol Cell Neurosci 2010 : Thus, although SKF activity is required to achieve AT(2) induced activation of TrkA, Rap1 and p42/p44(mapk), Fyn is essential for AT(2) receptor induced neurite outgrowth, but not in AT(2) signaling leading to p42/p44(mapk) activation
Teo et al., Nat Cell Biol 2010 : NF-kappaB is induced by ectopic expression of Rap1 , whereas its activity is inhibited by Rap1 depletion ... Furthermore, levels of Rap1 are positively regulated by NF-kappaB , and human breast cancers with NF-kappaB hyperactivity show elevated levels of cytoplasmic Rap1
Kim et al., Biochem Biophys Res Commun 2010 : In addition, IBMX induced PPAR-gamma transcriptional activity was blocked by PI3K/Akt, PKA, or Rap1 inhibitors
Lim et al., J Cell Biochem 2010 : Rap1 controls activation of the a ( M ) ß ( 2 ) integrin in a talin dependent manner
Awasthi et al., J Exp Med 2010 : However, absence of Rap1b impaired NKG2D , Ly49D, and NCR1 mediated cytokine and chemokine production
Iwasaki et al., Biochem Biophys Res Commun 2010 : PDZGEF2 induces activation of Rap1 and increases integrin mediated cell adhesion
Au-Yeung et al., Nat Immunol 2010 : In contrast, the catalytic activity of Zap70 was not required for activation of the GTPase Rap1 and inside-out signals that promote integrin adhesion
Tsalkova et al., Assay Drug Dev Technol 2011 : Our in vitro analyses using purified full-length Epac2 and Rap1 suggest that sulfonylureas are not able to directly bind to Epac2, nor are they capable of triggering Epac2 dependent Rap1 activation
Tao et al., Protein & cell 2010 : Evidence that the small GTPase Rap1 and its guanine exchange factor CalDAG-GEF1, together with RIAM, a Rap1GTP adaptor protein, promote the interaction of talin with the integrin ß subunit, has greatly contributed to fill the gap in our understanding of the signaling pathway from G-coupled agonist receptors and their phospholipase C-dependant second messengers, to integrin activation
Pertuit et al., Endocrinology 2011 : In this study on the conditional gsp-oncogene expressing GH4C1 cell line, expression of the gsp oncogene, which was observed in up to 40 % of GH-secreting adenomas, was found to induce sustained ERK1/2 activation, which required activation of the protein kinase A and the GTPases Ras and Rap1
Dong et al., Endocr Relat Cancer 2011 (Adenocarcinoma, Follicular...) : Histone deacetylase inhibitors upregulate Rap1GAP and inhibit Rap activity in thyroid tumor cells
Muramatsu et al., Nat Med 2011 (Encephalomyelitis, Autoimmune, Experimental...) : Binding of RGMa to CD4 ( + ) T cells led to activation of the small GTPase Rap1 and increased adhesion of T cells to intracellular adhesion molecule-1 ( ICAM-1 ) ... Binding of RGMa to CD4 ( + ) T cells led to activation of the small GTPase Rap1 and increased adhesion of T cells to intracellular adhesion molecule-1 ( ICAM-1 )
McSherry et al., Breast Cancer Res 2011 (Breast Neoplasms...) : Rap1 activity was reduced in response to JAM-A knockdown or inhibition, and pharmacological inhibition of Rap1 reduced MCF7 cell migration
Hernández-Varas et al., J Biol Chem 2011 (Melanoma...) : We show here that RIAM is expressed in metastatic human melanoma cells and that both RIAM and Rap1 are required for BLM melanoma cell invasion
Dzhura et al., Islets 2011 : Since the KO of PLC-e disrupts the ability of 8-pCPT-2'-O-Me-cAMP-AM to potentiate GSIS, while also disrupting its ability to stimulate an increase of ß-cell [ Ca2+ ] i, the available evidence indicates that it is a Rap1 regulated PLC-e that links Epac2 activation to Ca2+ dependent exocytosis of insulin
Matsumoto et al., Mol Med Report 2008 : In K1 cells, B-Raf might predominate over Raf-1, and the elevated cAMP is thought to promote MAPK phosphorylation through the PKA mediated activation of Rap1
Stadtmann et al., Eur J Immunol 2011 (Peritonitis) : Rap1a activation by CalDAG-GEFI and p38 MAPK is involved in E-selectin dependent slow leukocyte rolling ... Rap1a activation by CalDAG-GEFI and p38 MAPK is involved in E-selectin dependent slow leukocyte rolling ... Our data demonstrate that Rap1a activation by p38 MAPK and CalDAG-GEFI is involved in E-selectin dependent slow rolling and leukocyte recruitment ... Our data demonstrate that Rap1a activation by p38 MAPK and CalDAG-GEFI is involved in E-selectin dependent slow rolling and leukocyte recruitment
Kempf et al., Nat Med 2011 (Myocardial Infarction) : Mechanistically, GDF-15 counteracted chemokine triggered conformational activation and clustering of ß ( 2 ) integrins on PMNs by activating the small GTPase Cdc42 and inhibiting activation of the small GTPase Rap1
Jossin et al., Nat Neurosci 2011 : We found that Rap1 regulated the plasma membrane localization of NCad and NCad rescued radial polarization when Rap1 was inhibited ... We propose a multistep mechanism in which Reelin activates Rap1 , Rap1 upregulates NCad, and NCad is needed to orient cell migration
He et al., J Cell Sci 2011 : Depletion of Lyn in neutrophil-like HL-60 cells prevented chemoattractant induced Rap1 activation at the leading edge of the cell, whereas ectopic expression of Rap1 largely rescued the defects induced by Lyn depletion ... Furthermore, Lyn controls spatial activation of Rap1 by recruiting the CrkL-C3G protein complex to the leading edge
Lakshmikanthan et al., Blood 2011 : Rap1 promotes VEGFR2 activation and angiogenesis by a mechanism involving integrin avß3 ... Using ECs obtained from Rap1-deficient mice we demonstrate that Rap1b promotes VEGF-VEGFR2 kinase activation and regulates integrin activation ... Using ECs obtained from Rap1-deficient mice we demonstrate that Rap1b promotes VEGF-VEGFR2 kinase activation and regulates integrin activation ... Importantly, the Rap1b dependent VEGF-VEGFR2 activation is in part mediated via integrin a ( v ) ß ( 3 ) ... Importantly, the Rap1b dependent VEGF-VEGFR2 activation is in part mediated via integrin a ( v ) ß ( 3 ) ... These results provide a novel insight into the role of Rap1 in VEGF signaling in ECs
Frech et al., Science 1990 : Rap1A-p21 was not activated by GAP but bound tightly to GAP and was an effective competitive inhibitor of GAP mediated Ras-GTPase activity
Machtaler et al., J Cell Sci 2011 : Using shRNA knockdown of Cx43 in WEHI 231 cells, we show that Cx43 is required for sustained Rap1 activation and BCR mediated spreading ... Expression of wild-type Cx43-GFP, but not Cx43dT-GFP, was sufficient to restore sustained, BCR mediated Rap1 activation and cell spreading ... Expression of wild-type Cx43-GFP , but not Cx43dT-GFP, was sufficient to restore sustained, BCR mediated Rap1 activation and cell spreading
Vuchak et al., Cell Adh Migr 2011 (Colonic Neoplasms) : In previous studies we demonstrated that silencing Rap1GAP expression in human colon cancer cells resulted in sustained increases in Rap activity, enhanced spreading on collagen and the weakening of cell-cell contacts ... Overexpression of Rap1GAP in human colon cancer cells impaired Rap2 activity and the ability of cells to spread and migrate on collagen IV
Chang et al., Mol Cell Biol 2011 : We show that Epac1 and Rap1 , in response to cAMP, activate CaMKI to phosphorylate Ser47 in GCM1
Stefanini et al., Arterioscler Thromb Vasc Biol 2012 : Whereas Rap1 signaling directly controls sustained Rac1 activation, Rac1 affects CalDAG-GEFI- and P2Y12 dependent Rap1 activation via its role in calcium mobilization and granule/ADP release, respectively ... Whereas Rap1 signaling directly controls sustained Rac1 activation, Rac1 affects CalDAG-GEFI- and P2Y12 dependent Rap1 activation via its role in calcium mobilization and granule/ADP release, respectively
Yuen et al., Mol Cell Endocrinol 2012 : Optimized amplification and single-cell analysis identify GnRH mediated activation of Rap1b in primary rat gonadotropes
Bah et al., Nucleic Acids Res 2012 : RNA polymerase II (RNAPII) associates with pombe chromosome ends in vivo and the telomeric factor Rap1 negatively regulates this association, as well as the cellular accumulation of RNA emanating from chromosome ends
Li et al., J Huazhong Univ Sci Technolog Med Sci 2011 : VEGF stimulated Rap1 activity, phosphorylation of ERK and Akt, cyclin D1 expression and cell proliferation were repressed in HUVECs overexpressing Rap1GAP as compared to empty vector transfected control
Kim et al., J Biol Chem 2012 : Furthermore, 8CPT-2Me-cAMP increased the co-immunoprecipitation of profilin with Rap1 , whereas Tat-C3 toxin decreased that of profilin with RhoA
Banerjee et al., Small GTPases 2012 (Carcinoma, Squamous Cell...) : This microRNA controlled activation of Rap1, via EZH2 mediated silencing of Rap1GAP , is a novel mechanism of Rap1 regulation
Maymó et al., PloS one 2012 (MAP Kinase Signaling System) : In addition, the overexpression of Epac and Rap1 proteins increased leptin promoter activity and enhanced hCG
Tsalkova et al., Proc Natl Acad Sci U S A 2012 : These EAPC2-specific antagonists, designated as ESI-05 and ESI-07, inhibit Rap1 activation mediated by EAPC2, but not EPAC1 , with high potency in vitro
Liu et al., Mol Biol Cell 2012 : Overall, these studies establish that Radil regulates neutrophil adhesion and motility by linking Rap1 to ß2-integrin activation
Menon et al., PloS one 2012 (Neovascularization, Pathologic...) : Previous work from our laboratory showed that sustained stimulation of Rap1 by 8-pCPT-2'-O-Me-cAMP ( 8CPT ) via activation of Epac, a Rap1 GEF, or by expression of a constitutively active Rap1 mutant ( cRap1 ) suppresses endothelial cell chemotaxis and subsequent angiogenesis
Lackner et al., Dev Dyn 2013 : We propose a model in which Rap1b activates Integrin/Fibronectin receptors as part of an `` inside-out '' signaling pathway that promotes Integrin binding to FN, FN matrix assembly, and subsequent stabilization of morphological somite boundaries
Ahmed et al., J Cell Biol 2012 (Adenocarcinoma...) : KIF14 negatively regulates Rap1a-Radil signaling during breast cancer progression
Guimond et al., Eur J Pharmacol 2013 : As Ang II, C21/M024 induced a Rap1 dependent activation of p42/p44(mapk) whereas preincubation of cells with C38/M132 inhibited p42/p44(mapk) and Rap1 activation induced by Ang II ... As Ang II, C21/M024 induced a Rap1 dependent activation of p42/p44(mapk) whereas preincubation of cells with C38/M132 inhibited p42/p44(mapk) and Rap1 activation induced by Ang II ... As Ang II, C21/M024 induced a Rap1 dependent activation of p42/p44(mapk) whereas preincubation of cells with C38/M132 inhibited p42/p44(mapk) and Rap1 activation induced by Ang II ... As Ang II, C21/M024 induced a Rap1 dependent activation of p42/p44(mapk) whereas preincubation of cells with C38/M132 inhibited p42/p44(mapk) and Rap1 activation induced by Ang II
Cipolla et al., Journal of thrombosis and haemostasis : JTH 2013 : In fibrinogen-adherent platelets, both Pyk2 and PI3Kß were necessary for stimulation of the small GTPase Rap1b , a regulator of cell adhesion and spreading ... In fibrinogen-adherent platelets, both Pyk2 and PI3Kß were necessary for stimulation of the small GTPase Rap1b , a regulator of cell adhesion and spreading
Moore et al., Blood 2013 (Thrombocythemia, Essential) : Indeed, we found that platelets from JAK2V617F positive ET patients have significantly reduced phosphorylation of the PI3 kinase substrate Akt, and have reduced activation of Rap1 in response to thrombopoietin , IGF-1, ADP, SFLLRN, and thrombin ... Indeed, we found that platelets from JAK2V617F positive ET patients have significantly reduced phosphorylation of the PI3 kinase substrate Akt, and have reduced activation of Rap1 in response to thrombopoietin, IGF-1 , ADP, SFLLRN, and thrombin
Alemayehu et al., PloS one 2013 (Breast Neoplasms...) : Finally, we have identified that LPA enhances the binding of endogenous Rap1A to ß-arrestin2, and also stimulates Rap1A and IQGAP1 to associate with LPA ( 1 )
Utreras et al., Neurochem Int 2013 : Cdk5 regulates Rap1 activity
Takino et al., Cell Adh Migr 2013 : Furthermore, RasGRP2 overexpression increased Rap1 activation and cell-matrix adhesion in ECV304 cells
Schmid et al., PloS one 2013 (Inflammation...) : Genetic depletion of PLC?, CalDAG-GEFI or II, Rap1a , or the Rap1 effector RIAM was sufficient to prevent integrin a4 activation by chemoattractants or activated PI3K? ( p110?CAAX ), while activated Rap ( RapV12 ) promoted constitutive integrin activation and cell adhesion that could only be blocked by inhibition of RIAM or integrin a4ß1
Guidetti et al., Biochem J 2013 : In blood platelets the small GTPase Rap1b is activated by cytosolic Ca2+ and promotes integrin aIIbß3 inside-out activation and platelet aggregation ... In transfected HEK ( human embryonic kidney ) -293 cells, as well as in platelets, forskolin induced phosphorylation of CalDAG-GEFI prevented the activation of Rap1b induced by the Ca2+ ionophore A23187
Subramanian et al., Journal of thrombosis and haemostasis : JTH 2013 (Calcium Signaling) : Phosphorylation of CalDAG-GEFI by protein kinase A prevents Rap1b activation ... Phosphorylation of S587 correlated with the inhibitory effect of PKA on Rap1b activation in platelets
Birukova et al., Mol Biol Cell 2013 : We tested a hypothesis that Rho down-regulation and barrier recovery of agonist stimulated ECs is mediated by the Ras family GTPase Rap1 ... Thrombin induced EC permeability driven by rapid activation of the Rho GTPase pathway was followed by Src kinase dependent phosphorylation of the Rap1-specific guanine nucleotide exchange factor (GEF) C3G, activation of Rap1 , and initiation of EC barrier recovery ... Knockdown experiments showed that Rap1 activation was essential for down-regulation of Rho signaling and actin stress fiber dissolution ... This mechanism also included Rap1 dependent membrane translocation of the Rac1-specific GEF Tiam1 and activation of Rac1 dependent peripheral cytoskeletal dynamics, leading to resealing of intercellular gaps
Graham et al., Mol Microbiol 1994 : A Reb1p binding site is required for efficient activation of the yeast RAP1 gene, but multiple binding sites for Rap1p are not essential ... These data confirm that Rap1p is not required for activation of the RAP1 gene, and suggest a role for Rap1p in negative autoregulation
Janoueix-Lerosey et al., Biochem Biophys Res Commun 1994 : This phosphorylation does not affect the stimulation of the GTPase activity of Rap1 by Rap1GAP but may play a role in regulating the interaction of Rap1GAP with other proteins involved in the cellular functions regulated by Rap1 and Rap1GAP
Ohtsuka et al., J Biol Chem 1996 : Here we have used this assay system and examined the effect of Rap1 on the B-Raf activity to phosphorylate recombinant MAP kinase kinase ( MEK ) ... Recombinant Rap1B stimulated the activity of B-Raf , which was partially purified from bovine brain and immunoprecipitated by an anti-B-Raf antibody ... Rap1B enhanced the Ki-Ras stimulated B-Raf activity in an additive manner
Kuroda et al., J Biol Chem 1996 : Different effects of various phospholipids on Ki-Ras-, Ha-Ras-, and Rap1B induced B-Raf activation ... Moreover, we found that Rap1B as well as Ki-Ras and Ha-Ras stimulate the B-Raf activity ... Since B-Raf contains a cysteine-rich domain originally found in protein kinase C as a domain responsible for interaction with phosphatidylserine ( PS ) and diacylglycerol or 12-O-tetradecanoylphorbol-13-acetate, we have examined here the effect of these compounds on the Ki-Ras-, Ha-Ras-, and Rap1B induced activation of bovine brain B-Raf ... However, none of the above phospholipids affected the Ha-Ras stimulated B-Raf activity, whereas PI, PS, phosphatidylethanolamine, and phosphatidic acid inhibited the Rap1B stimulated B-Raf activity ... Phosphatidylcholine or PI-4-monophosphate did not show any effect on the Rap1B stimulated B-Raf activity ... Synthetic PS with two unsaturated fatty acids, such as 1,2-dioleoyl-PS or 1,2-dilinoleoyl-PS, showed the same effect toward the Ki-Ras- and Rap1B stimulated B-Raf activities, but synthetic PS with two saturated fatty acids, such as 1, 2-distearoyl-PS, was inactive ... 12-O-Tetradecanoylphorbol-13-acetate did not affect the stimulatory or inhibitory effect of PS on the Ki-Ras- and Rap1B stimulated B-Raf activities, respectively ... These results indicate that various phospholipids differently affect Ki-Ras-, Ha-Ras, and Rap1B induced B-Raf activation
Vossler et al., Cell 1997 : These cell type-specific actions of cAMP require the expression of the serine/threonine kinase B-Raf and activation of the small G protein Rap1 ... Rap1 , activated by mutation or by the cAMP dependent protein kinase PKA, is a selective activator of B-Raf and an inhibitor of Raf-1 ... Rap1 , activated by mutation or by the cAMP dependent protein kinase PKA, is a selective activator of B-Raf and an inhibitor of Raf-1
Hu et al., J Biol Chem 1997 : However, Rap1A , which has an identical effector domain to that of Ras, can not activate Raf-1 and even antagonizes several Ras functions in vivo
Hattori et al., Gan To Kagaku Ryoho 1997 (Cell Transformation, Neoplastic) : [ Activation of Rap1 , antagonist to ras, by Crk-C3G ]
Okada et al., J Biol Chem 1997 : Insulin and epidermal growth factor stimulate a conformational change in Rap1 and dissociation of the CrkII-C3G complex ... Insulin and epidermal growth factor stimulate a conformational change in Rap1 and dissociation of the CrkII-C3G complex
Wolthuis et al., Mol Cell Biol 1998 : This activation mechanism correlates with the activation mechanism of the small GTPase Rap1 , a putative upstream regulator of Ral guanine nucleotide exchange factors
M'Rabet et al., Blood 1998 : Finally, we found that Rap1 is activated by both the Ca2+ ionophore ionomycin and the phorbol ester 12-O-tetradecanoylphorbol 13-acetate ( TPA ), indicating that phospholipase C (PLC) activation leading to elevated levels of intracellular free Ca2+ and diacylglycerol ( DAG ) can mediate Rap1 activation
Zwartkruis et al., EMBO J 1998 : In addition, we found that although overexpression of active Rap1 is able to activate the Ral pathway, activation of endogenous Rap1 in fibroblasts does not result in Ral activation
McLeod et al., J Biol Chem 1998 : In this report, we show that BCR engagement activates Rap1 and that this is dependent on production of diacylglycerol ( DAG ) by phospholipase C-gamma ... Activation of Rap1 by the BCR was greatly reduced in phospholipase C-gamma-deficient B cells, whereas both a synthetic DAG and phorbol dibutyrate could activate Rap1 in B cells ... However, the DAG dependent pathway by which the BCR activates Rap1 apparently does not involve Crk signaling complexes since phorbol dibutyrate could activate Rap1 without inducing the formation of these complexes ... Thus, the BCR activates Rap1 via a novel DAG dependent pathway
Kawasaki et al., Proc Natl Acad Sci U S A 1998 : Expression of CalDAG-GEFI activates Rap1A and inhibits Ras dependent activation of the Erk/MAP kinase cascade in 293T cells ... We propose that CalDAG-GEF proteins have a critical neuronal function in determining the relative activation of Ras and Rap1 signaling induced by Ca2+ and DAG mobilization
Hu et al., J Biol Chem 1999 : Effect of phosphorylation on activities of Rap1A to interact with Raf-1 and to suppress Ras dependent Raf-1 activation
Hilairet et al., Neuropeptides 1998 : In these cells, VIP induces Rap 1 phosphorylation and a yet unidentified modification that leads to their acidification