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] a74 f20 b95 d24 d71 ecb a36 c2b b12 Stathmin is a ubiquitous phsosphorylated protein https://en.wikipedia.org/wiki/Stathmin#Function parentid=P19419; position=ser389; ptm=p; direction=u parentid=P19419; position=ser383; ptm=p; direction=u parentid=P19419; position=ser324; ptm=p; direction=u Presumably a deactivating phosphorylation event, since JNK phosphorylaiton is shown as inhibitory parentid=P61224; parentsymbol=RAP1B; site=PGKARKKsscQLL; position=ser179; sitegrpid=451799; ptm=p; direction=u parentid=O14920; position=ser181; ptm=p; direction=u https://en.wikipedia.org/wiki/I%CE%BAB_kinase#Regulation parentid=O14920; position=ser177; ptm=p; direction=u G2019S parentid=Q02750; parentsymbol=MAP2K1; site=LIDsMANsFVGTRSY; position=ser222; sitegrpid=448513; ptm=p; direction=u parentid=Q02750; parentsymbol=MAP2K1; site=VsGQLIDsMANsFVG; position=ser218; sitegrpid=448514; ptm=p; direction=u parentid=P28482; parentsymbol=MAPK1; site=HDHtGFLtEyVAtRW; position=thr185; sitegrpid=447593; ptm=p; direction=u parentid=P28482; parentsymbol=MAPK1; site=HtGFLtEyVAtRWyR; position=tyr187; sitegrpid=447594; ptm=p; direction=u parentid=P27361; parentsymbol=MAPK3; site=HDHtGFLtEyVAtRW; position=thr202; sitegrpid=447542; ptm=p; direction=u parentid=P27361; parentsymbol=MAPK3; site=HtGFLtEyVAtRWyR; position=tyr204; sitegrpid=447543; ptm=p; direction=u parentid=P05412; position=ser73; ptm=p; direction=u parentid=P05412; position=ser63; ptm=p; direction=u https://en.wikipedia.org/wiki/I%CE%BAB_kinase#Regulation parentid=O15111; position=thr23; ptm=p; direction=u Presumably a deactivating phosphorylation event, since JNK phosphorylaiton is shown as inhibitory parentid=P36507; parentsymbol=MAP2K2; site=LIDsMANsFVGTRSY; position=ser226; sitegrpid=448074; ptm=p; direction=u parentid=P36507; parentsymbol=MAP2K2; site=VsGQLIDsMANsFVG; position=ser222; sitegrpid=448073; ptm=p; direction=u parentid=P04049; parentsymbol=RAF1; site=IGDFGLAtVksRWsG; position=thr491; sitegrpid=447748; ptm=p; direction=u parentid=P04049; parentsymbol=RAF1; site=RPRGQRDssyyWEIE; position=ser338; sitegrpid=447742; ptm=p; direction=u ea5 e69 12849693 PubMed Silica induces nuclear factor-kappaB activation through TAK1 and NIK in Rat2 cell line. Toxicol Lett 2003 Cho H Lee J Kwak NJ Lee KH Rha S Kim YH Cho YY Yang KH Kim K Lim Y 12191611 PubMed Docking interactions in the mitogen-activated protein kinase cascades. Pharmacol Ther 2002 Tanoue T Nishida E 11749383 PubMed MAP kinases. Chem Rev 2001 Chen Z Gibson TB Robinson F Silvestro L Pearson G Xu B Wright A Vanderbilt C Cobb MH MAPK signaling pathway PW:0000007 Pathway Ontology mitogen activated protein kinase signaling pathway PW:0000007 Pathway Ontology 12566928 PubMed The role of mitogen-activated protein kinase pathways in Alzheimer's disease. Neurosignals 2002 Zhu X Lee HG Raina AK Perry G Smith MA 17726008 PubMed MEKK4 stimulation of p38 and JNK activity is negatively regulated by GSK3beta. J Biol Chem 2007 Abell AN Granger DA Johnson GL 22539006 PubMed (G2019S) LRRK2 activates MKK4-JNK pathway and causes degeneration of SN dopaminergic neurons in a transgenic mouse model of PD. Cell Death Differ 2012 Chen CY Weng YH Chien KY Lin KJ Yeh TH Cheng YP Lu CS Wang HL 12676795 PubMed Trk receptors: roles in neuronal signal transduction. Annu Rev Biochem 2003 Huang EJ Reichardt LF 11369511 PubMed Signalling for survival and death in neurones: the role of stress-activated kinases, JNK and p38. Cell Signal 2001 Harper SJ LoGrasso P 14597384 PubMed Transcriptional regulation by the MAP kinase signaling cascades. Gene 2003 Yang SH Sharrocks AD Whitmarsh AJ 12947395 PubMed MAPK pathways in radiation responses. Oncogene 2003 Dent P Yacoub A Fisher PB Hagan MP Grant S 12390245 PubMed Neuronal p38 MAPK signalling: an emerging regulator of cell fate and function in the nervous system. Genes Cells 2002 Takeda K Ichijo H