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ACD — PARP1
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