Gene interactions and pathways from curated databases and text-mining

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Pathways - manually collected, often from reviews:

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

Studies that report less than 10 interactions are marked with *

Text-mined interactions from Literome

Yue et al., Curr Biol 2004 : The MAPK activator MEK1 is required for mitotic activation of p42 MAPK in Xenopus egg extracts ; however, the identity of the kinase that activates MEK1 is unknown
Huwiler et al., Br J Pharmacol 1994 : 2. Both nucleotides stimulate phosphorylation and activation of mitogen activated protein kinase and a biphasic phosphorylation of the up-stream mitogen activated protein kinase kinase
Tu et al., J Biomed Sci 2001 (Carcinoma, Hepatocellular) : On the other hand, PD98059, a specific inhibitor of mitogen activated protein kinase kinase , blocks TPA induced MAPK activation but has no effect on TPA induced tyrosine phosphorylation
Zhang et al., Arterioscler Thromb Vasc Biol 2005 (Vasculitis) : In contrast, mitogen activated protein kinase kinase-1 ( MEK1 ) inhibition ( dominant negative MEK1 adenovirus or inhibitor U0126 ) suppressed Ang II-induced NF-kappaB promoter activity, NF-kappaB DNA binding activity, p65 phosphorylation, and led to 70 % reduction in IL-6 transcription/production
Castoria et al., EMBO J 1999 (Breast Neoplasms) : Furthermore, the selective MEK 1 inhibitor, PD 98059, inhibits oestradiol and progestin stimulation of Erk-2 and the steroid dependent S-phase entry
Iwata et al., J Biol Chem 2001 (MAP Kinase Signaling System) : Transfection of constitutively active MEK-1 resulted in MAPK phosphorylation in alpha-synuclein expressing cells and improved cell viability even under reduced serum conditions
Nantel et al., J Biol Chem 1998 : Interaction of Grb10 with Raf1 is constitutive, while interaction between Grb10 and MEK1 needs insulin treatment of the cells and follows mitogen activated protein kinase activation
Rose et al., J Immunol 1997 : The selective MAPK/extracellular signal regulated kinase-1 ( MEK-1 ) inhibitor PD 098059 inhibited activation of p42MAPK induced by Fc gamma R cross linking, but not p38 or JNK/SAPK activation
Lee et al., J Cell Physiol 2006 : TNF-alpha enhanced expression of VCAM-1 protein and mRNA as well as phosphorylation of p42/p44 MAPK , p38, and JNK were significantly attenuated by inhibitors of MEK1/2 ( U0126 ), p38 ( SB202190 ), and JNK ( SP600125 )
Mansour et al., Biochemistry 1996 : Both the acidic substitutions and the N-terminal deletion increase Vmax, V/K ( m ), ERK2 , and V/K ( m ), ATP, as is also observed following phosphorylation of wild-type MKK1
Aroor et al., Alcohol 2009 : These results suggest that Ang II-mediated accumulation of phospho-p42/44 MAPK in the hepatocyte nucleus involves MEK 1/2 dependent activation and this effect is potentiated by ethanol
Chien et al., Biochem Biophys Res Commun 2006 (Lung Neoplasms) : SB203580, a p38 MAPK inhibitor, but not PD098059 and SP600125, specific inhibitor of MKK1 and selective inhibitor of JNK, respectively, suppressed COX-2 expression
Ho et al., J Neurochem 1997 : Mobility shift, phosphoepitope analysis, and direct measurement of kinase activity indicated that the Mek1 inhibitor dose-dependently blocked basal and okadaic acid induced MAPK activation
Kim et al., IUBMB Life 2000 : S1P treatment transiently activated Erk-1/-2 in a dose dependent manner, and its activation was blocked by pertussis toxin, expression of RasN17, or inhibition of Raf or MEK-1/-2
McKinstry et al., Cancer Biol Ther 2002 (Breast Neoplasms...) : Inhibition of MEK1/2 caused modest reductions in basal MAPK activity and transiently suppressed UCN-01 stimulated MAPK activity below that of MEK1/2 inhibitor alone
Boyd et al., Neuropharmacology 2002 : Using two structurally distinct inhibitors of the activation of MEK1 ( mitogen activated protein ( MAP) kinase kinase 1 ), PD 98059 and U 0126, we have shown that the MAP kinase signalling cascade does not appear to underlie muscarinic inhibition of IK ( SO ), recorded using whole-cell patch-clamp methods
Hayashi et al., Eur Respir J 2000 : Lung fibroblasts were stimulated with BK in the presence or in the absence of PD98059, a specific MAPK/ERK kinase-1 inhibitor, or SB203580, a specific p38 MAPK inhibitor , and IL-6 or IL-8 production and their gene expression was examined
Gardner et al., J Biol Chem 1996 : Pharmacological inhibition of MEK-1 activity by incubation of cells with the compound PD 098059 blocked p42(MAPK) activation and FGF-2 protection against apoptosis
Hashimoto et al., Life Sci 1999 : To this end, we examined changes in cellular morphology and MAPK activation in NE-stimulated BEC monolayer, and the effect of PD 98059 as the specific inhibitor for MAPK kinase-1 ( MEK-1 , the upstream regulator of MAPK ) on NE-induced changes in cellular morphology and MAPK activation
Klegeris et al., FASEB J 2006 (Astrocytoma...) : It is also attenuated by PD 98059, an inhibitor of the MAPK/extracellular regulated kinase kinase MEK1/2 , SP 600125, an inhibitor of c-Jun N-terminal kinase (JNK), and SB 202190, an inhibitor of p38 MAPK
Hayashi et al., Hepatology 2000 : Moreover, the MAPK/ERK activation by HCV core protein was blocked in the presence of the specific MEK1 inhibitor, PD98059
Yu et al., Oncogene 2004 (Leukemia) : These events were accompanied by the caspase independent downregulation of Raf-1, inactivation of MEK1/2 , ERK, Akt, p70S6K, dephosphorylation of GSK-3, and activation of c-Jun-N-terminal kinase (JNK) and p38 MAPK
Wu et al., Cell Microbiol 2006 (MAP Kinase Signaling System) : Our results showed that phosphorylated mitogen activated protein kinase ( MAPK ) kinase ( MEK) 1/2, p44/p42 MAPK and p90 ribosomal S6 kinase (p90RSK) were observed and this pathway was inhibited by MEK1/2 inhibitors U0126 and PD98059
Mukherjee et al., Carcinogenesis 2006 (Chromosomal Instability) : Activation of both ERKs and p38 MAPK by BPDE and attenuation of BPDE induced p53 accumulation by U0126 or SB202190, specific inhibitor of MEK1/2 or p38 MAPK, indicate the role of ERKs and p38 MAPK in p53 accumulation
McDuffie et al., J Cardiovasc Pharmacol 2000 : The agonist stimulated phosphorylation of MAPK was blocked by the 5-HT1b-receptor antagonist isamoltane ( 0.01-10 p3M ) and the MEK-1 inhibitor PD 098059 ( [ 2- ( 2'-amino-3'-methoxy-phenyl ) -oxanaphthalen-4-one ] ; 0.01-10 microM¿
Tseng et al., Biochem Biophys Res Commun 2001 : To determine the involvement of MEK1-p42/p44 MAPK pathway in mediating DAB2 gene expression, we have performed the following experiments and found that ( i ) there was sustained activation of p42/p44 MAPK , but not p38 MAPK, upon K562 cells differentiation ; ( ii ) application of MEK1 inhibitor U0126 reduced the expression of DAB2 protein, mRNA and promoter activity, as well as cell differentiation ; ( iii ) constitutively active MEK1 increased DAB2 promoter activity ; and ( iv ) dominant negative ERK2 abolished constitutively active MEK1 induced DAB2 promoter activity
Liu et al., PloS one 2010 : Expression of constitutively active MKK1 also attenuated rapamycin inhibition of IGF-1 stimulated phosphorylation of Erk1/2 and cell motility
Park et al., Mol Cancer Ther 2008 (Carcinoma, Hepatocellular...) : Inhibition of p38 MAPK or knockdown of BID, FAS associated death domain, or CD95 expression suppressed MEK1/2 inhibitor and 17AAG lethality
Learish et al., Brain Res Dev Brain Res 2000 : These data provide evidence that activation of MAPK by MEK1 is important for the proliferation of NP cells
Huang et al., Biochem Biophys Res Commun 2003 : MAP3Ks are components of a three tiered protein kinase pathway in which a MAP3K phosphorylates and activates a mitogen activated protein kinase kinase ( MAP2K ), which in turn activates a mitogen activated protein kinase ( MAPK )
Martel-Pelletier et al., Arthritis Rheum 1999 (Osteoarthritis) : Within minutes, IL-17 induced the phosphorylation of mitogen activated protein kinase kinase-1/2 ( MEK-1/2 ), -3/6 ( MKK-3/6 ), p44/42, p38, and inhibitor of nuclear factor kappaB ( I kappaB)-alpha, as well as the activation of mitogen activated protein kinase activated protein kinase-1 and -2 ( MAPKAPK-1 and -2 ) ... Within minutes, IL-17 induced the phosphorylation of mitogen activated protein kinase kinase-1/2 ( MEK-1/2 ), -3/6 ( MKK-3/6 ), p44/42, p38, and inhibitor of nuclear factor kappaB ( I kappaB)-alpha, as well as the activation of mitogen activated protein kinase activated protein kinase-1 and -2 ( MAPKAPK-1 and -2 )
Giannopoulou et al., American journal of physiology. Renal physiology 2006 (Fibrosis...) : Constitutive activation of Erk-1/2 by ectopic expression of activated Mek1 mimicked IFN-gamma and suppressed TGF-beta(1) mediated alpha-SMA expression
Sananbenesi et al., J Neurosci 2003 (MAP Kinase Signaling System) : Intrahippocampal injection of the selective Mek-1/2 inhibitor U0126 or CRF2 antagonist antisauvagine-30 ( aSvg-30 ) prevented stress enhanced fear conditioning and Mek-1/2 dependent activation of Erk-1/2 and p90Rsk-1
Pike et al., Cell Signal 2013 : Truncated MEK1 is required for transient activation of MAPK signalling in G2 phase cells
Waas et al., Biochemistry 2003 : To do this, ERK2 was quantitatively activated by MAPKK1 in vitro by monitoring the stoichiometry and site specificity of phosphorylation using a combination of protein mass spectrometry, tryptic peptide analysis, and ( 32 ) P radiolabeling
Bazan et al., Curr Eye Res 1997 : Corneal tissue expresses ERK2 or MAPK, and both MEK1 and MEK2, the immediate upstream regulators of MAPK
Malarkannan et al., J Immunol 2012 : This includes actin polymerization, tubulin multimerization, microtubule organizing center formation, calcium/calmodulin signaling, Pak/Raf/Mek1/2 mediated Erk1/2 activation , formation of maestrosome, E-cadherin, and CD44 mediated signaling and glycogen synthase kinase-3/adenomatous polyposis coli mediated ß-catenin activation
Denis-Henriot et al., Endocrinology 1998 : Wild-type Galpha12 overexpression prevented the decrease in MAPK activity and induced MEK1 , but not B-Raf, expression
Tsatsanis et al., Oncogene 1998 (Lymphoma, T-Cell) : Since the activation of NFAT is MAPK dependent these findings suggested that the activation of MAPK by Tpl-2 is either independent or only partially dependent on MEK1 and MEK2
Hu et al., J Biol Chem 2006 : Conversely, overexpression of constitutively activated Mek1 induced Erk-1/2 phosphorylation and MMP-9 expression
Newton et al., Br J Pharmacol 2000 : We have therefore used these cells to examine the effect of the selective mitogen activated protein ( MAP ) kinase inhibitors ; PD098059, a mitogen activated and extracellular regulated kinase kinase ( MEK) 1 inhibitor , UO126, a dual MEK1 & MEK2 inhibitor, and SB203580, a p38 MAP kinase inhibitor in the IL-1beta dependent release of PGE ( 2 )
Gire et al., Oncogene 1999 : Conversely, selective activation of MAPK by a constitutively-active MAPKK1 mutant failed to mimic the action of Ras and, although this was achievable with activated Raf, micro-injection of anti-ras antibodies showed that this still required endogenous wild-type Ras function
Pluskota et al., Eur J Biochem 2000 (MAP Kinase Signaling System) : The MEK-1 inhibitor PD 98059 blocked ERK-1/2 phosphorylation, and treatment of endothelial cells with PD 98059 resulted in apoptosis even upon Fg : ICAM-1 ligation
Winston et al., J Biol Chem 1995 : Preferential involvement of MEK1 in the tumor necrosis factor-alpha induced activation of p42mapk/erk2 in mouse macrophages
Tartaglia et al., Molecular syndromology 2010 : SHP2 ( encoded by PTPN11 ), SOS1, BRAF, RAF1 and MEK1 positively contribute to RAS-MAPK signaling, and possess complex autoinhibitory mechanisms that are impaired by mutations
de Bernardo et al., J Neurochem 2004 : MEK-1/2 and lipoxygenase (LOX) inhibitors, as well as ascorbic acid, prevent ERK-1/2 activation and neuronal loss, but the inhibition of nitric oxide sintase (NOS), cyclo-oxygenase (COX), c-Jun N-terminal kinase (JNK) and p38 mitogen activated protein kinase ( p38 MAPK ) does not have protective effects
Tao et al., Biochem J 2002 : We present data showing that overexpression of the serine threonine kinase, mitogen activated protein kinase/extracellular-signal regulated kinase kinase kinase-1 ( MEKK1 ), but not nuclear factor-kappa B inducing kinase, or MAP kinase/ERK kinase-1 (MEK1) , can significantly increase the level of CD28RE/AP1-driven luciferase ( Luc ) reporter gene expression in Jurkat E6-1 cells
Bajpai et al., Invest Ophthalmol Vis Sci 2007 (Anoxia...) : Inhibition of MEK1 by pharmacologic and dominant negative mutant approaches attenuated 15 ( S ) -HETE induced phosphorylation of ERK1/2 and JNK1 but not p38 MAPK
Daum et al., FEBS Lett 1998 : Pervanadate inhibits mitogen activated protein kinase kinase-1 in a p38MAPK dependent manner
Minelli et al., Peptides 2006 : It greatly enhances the phosphorylation of hsp27, alpha-B-crystallin, Cdc2, and p-38 MAPK , whereas it decreases the phosphorylation of MEK1 , Cav 2, GSK3a, PKB/Akt, PKCdelta, PKCgamma, and Erk2
Gardner et al., Mol Biol Cell 1994 : Raf and MAPK/extracellular signal regulated kinase kinase ( MEKK ) independently phosphorylate and activate MEK-1
Genot et al., EMBO J 1996 : Constitutively active MAPKK-1 fully activates ERK-2 and the transcription factor Elk-1, but does not substitute for activated p21ras and synergize with calcium/calcineurin signals to induce NFAT
Choi et al., Cancer Res 2001 (Glioblastoma...) : Herein, we demonstrate that : ( a ) stimulation with agonistic anti-Fas monoclonal antibody CH-11 and human recombinant soluble Fas ligand induces expression of the CC chemokine MCP-1 and the CXC chemokine interleukin-8 by human glioma cell lines at the mRNA and protein levels in a dose- and time dependent manner ; ( b ) selective pharmacological inhibitors of MEK1 ( U0126 and PD98059 ) and p38 mitogen activated protein kinase ( MAPK ) ( SB202190 ) suppress Fas mediated chemokine expression in a dose dependent manner ; ( c ) Fas ligation on human glioma cells leads to activation of both extracellular signal regulated kinases ERK1/ERK2 and p38 MAPK ; and ( d ) GBM samples express higher levels of Fas compared with normal control brain, which correlates with increased interleukin 8 expression
Braz et al., J Cell Biol 2002 (Cardiomyopathy, Hypertrophic) : A mechanism whereby PKC alpha might regulate hypertrophy was suggested by the observations that wild-type PKC alpha induced extracellular signal regulated kinase1/2 ( ERK1/2 ), that dominant negative PKC alpha inhibited PMA induced ERK1/2 activation, and that dominant negative MEK1 ( up-stream of ERK1/2 ) inhibited wild-type PKC alpha induced hypertrophic growth
Keeton et al., Biochim Biophys Acta 2004 (Carcinoma, Hepatocellular...) : Inhibition of MEK1 significantly inhibited extracellularly regulated kinase (ERK)1/2 activation and insulin regulated Gene33 transcription and protein levels in H4IIE cells