The mitogen-activated protein kinase (MAPK) cascade is a highly conserved module that is involved in various cellular functions, including cell proliferation, differentiation and migration. Mammals express at least four distinctly regulated groups of MAPKs, extracellular signal-related kinases (ERK)-1/2, Jun amino-terminal kinases (JNK1/2/3), p38 proteins (p38alpha/beta/gamma/delta) and ERK5, that are activated by specific MAPKKs: MEK1/2 for ERK1/2, MKK3/6 for the p38, MKK4/7 (JNKK1/2) for the JNKs, and MEK5 for ERK5. Each MAPKK, however, can be activated by more than one MAPKKK, increasing the complexity and diversity of MAPK signalling. Presumably each MAPKKK confers responsiveness to distinct stimuli. For example, activation of ERK1/2 by growth factors depends on the MAPKKK c-Raf, but other MAPKKKs may activate ERK1/2 in response to pro-inflammatory stimuli.
Description reference: KEGG http://www.genome.jp/dbget-bin/www_bget?pathway:map04010
Proteins on this pathway have targeted assays available via the [https://assays.cancer.gov/available_assays?wp_id=WP382 CPTAC Assay Portal]a74f20b95d24d71ecba36c2bb12Stathmin is a ubiquitous phsosphorylated proteinhttps://en.wikipedia.org/wiki/Stathmin#Functionparentid=P19419; position=ser389; ptm=p; direction=uparentid=P19419; position=ser383; ptm=p; direction=uparentid=P19419; position=ser324; ptm=p; direction=uPresumably a deactivating phosphorylation event, since JNK phosphorylaiton is shown as inhibitoryparentid=P61224; parentsymbol=RAP1B; site=PGKARKKsscQLL; position=ser179; sitegrpid=451799; ptm=p; direction=uparentid=O14920; position=ser181; ptm=p; direction=uhttps://en.wikipedia.org/wiki/I%CE%BAB_kinase#Regulationparentid=O14920; position=ser177; ptm=p; direction=uG2019Sparentid=Q02750; parentsymbol=MAP2K1; site=LIDsMANsFVGTRSY; position=ser222; sitegrpid=448513; ptm=p; direction=uparentid=Q02750; parentsymbol=MAP2K1; site=VsGQLIDsMANsFVG; position=ser218; sitegrpid=448514; ptm=p; direction=uparentid=P28482; parentsymbol=MAPK1; site=HDHtGFLtEyVAtRW; position=thr185; sitegrpid=447593; ptm=p; direction=uparentid=P28482; parentsymbol=MAPK1; site=HtGFLtEyVAtRWyR; position=tyr187; sitegrpid=447594; ptm=p; direction=uparentid=P27361; parentsymbol=MAPK3; site=HDHtGFLtEyVAtRW; position=thr202; sitegrpid=447542; ptm=p; direction=uparentid=P27361; parentsymbol=MAPK3; site=HtGFLtEyVAtRWyR; position=tyr204; sitegrpid=447543; ptm=p; direction=uparentid=P05412; position=ser73; ptm=p; direction=uparentid=P05412; position=ser63; ptm=p; direction=uhttps://en.wikipedia.org/wiki/I%CE%BAB_kinase#Regulationparentid=O15111; position=thr23; ptm=p; direction=uPresumably a deactivating phosphorylation event, since JNK phosphorylaiton is shown as inhibitoryparentid=P36507; parentsymbol=MAP2K2; site=LIDsMANsFVGTRSY; position=ser226; sitegrpid=448074; ptm=p; direction=uparentid=P36507; parentsymbol=MAP2K2; site=VsGQLIDsMANsFVG; position=ser222; sitegrpid=448073; ptm=p; direction=uparentid=P04049; parentsymbol=RAF1; site=IGDFGLAtVksRWsG; position=thr491; sitegrpid=447748; ptm=p; direction=uparentid=P04049; parentsymbol=RAF1; site=RPRGQRDssyyWEIE; position=ser338; sitegrpid=447742; ptm=p; direction=uea5e6912849693PubMedSilica induces nuclear factor-kappaB activation through TAK1 and NIK in Rat2 cell line.Toxicol Lett2003Cho HLee JKwak NJLee KHRha SKim YHCho YYYang KHKim KLim Y12191611PubMedDocking interactions in the mitogen-activated protein kinase cascades.Pharmacol Ther2002Tanoue TNishida E11749383PubMedMAP kinases.Chem Rev2001Chen ZGibson TBRobinson FSilvestro LPearson GXu BWright AVanderbilt CCobb MHMAPK signaling pathwayPW:0000007Pathway Ontologymitogen activated protein kinase signaling pathwayPW:0000007Pathway Ontology12566928PubMedThe role of mitogen-activated protein kinase pathways in Alzheimer's disease.Neurosignals2002Zhu XLee HGRaina AKPerry GSmith MA17726008PubMedMEKK4 stimulation of p38 and JNK activity is negatively regulated by GSK3beta.J Biol Chem2007Abell ANGranger DAJohnson GL22539006PubMed(G2019S) LRRK2 activates MKK4-JNK pathway and causes degeneration of SN dopaminergic neurons in a transgenic mouse model of PD.Cell Death Differ2012Chen CYWeng YHChien KYLin KJYeh THCheng YPLu CSWang HL12676795PubMedTrk receptors: roles in neuronal signal transduction.Annu Rev Biochem2003Huang EJReichardt LF11369511PubMedSignalling for survival and death in neurones: the role of stress-activated kinases, JNK and p38.Cell Signal2001Harper SJLoGrasso P14597384PubMedTranscriptional regulation by the MAP kinase signaling cascades.Gene2003Yang SHSharrocks ADWhitmarsh AJ12947395PubMedMAPK pathways in radiation responses.Oncogene2003Dent PYacoub AFisher PBHagan MPGrant S12390245PubMedNeuronal p38 MAPK signalling: an emerging regulator of cell fate and function in the nervous system.Genes Cells2002Takeda KIchijo H