Mapk signaling pathway (Mus musculus)

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1, 3-122Proliferation, inflammation, anti-apoptosisDNAJNK & p38 MAP kinase pathwayCycleCa2+Wnt signaling pathwayMAPKKKKERK5 pathwayMKPProliferation, differentiationCellProliferation, differentiation,inflammationDNASerum, cytotoxic drugs, irradiation, heatshock, reactive oxy speciesLPS and other stressPTPDNAHeteromeric G-proteinJNKDNAMAPKKTranscription factorsClassical MAP kinase PathwayDNALPSDAGProliferation, differentiationIP3ApoptosisMAPKKKp53 signaling pathwaySerum, EGF,reactive oxygen species.or Srk tyrokinase downstreamDNA damageMAPKPTPp38Phosphatidylinositolsignaling systemAkt3Dusp7Gadd45aPla2g5PtprrAkt2Akt1PrkcbPrkczDdit3MEKK2/3Mapk4Ptpn7Dusp1fgfrPpp5cMap3k13PrkccRap1aPrkcdTraf6Mapk8ip3Tmem37Mapk1FosAtf4Rasa1EgfrElk1Map4k1PrkacaDusp10DaxxRps6ka3Stk3Trp53Map2k1CrklDusp4Ntf5Map4k4FasHspa5Taok2Arrb2Rap1bIkbkgcAMPMink1Il1aFaslCdc42Map2k1|P1Cd14Taok1JunMap3k12Tgfbr2MrasMaxHspa8JundPtpn7CrkMap3k7ip2Traf2Map3k8FlnaGna12Pak2Casp6Map2k2Acvr1bPdgfrbCasp3Mef2cBdnfTgfb3Rac1Casp9Casp2Casp7Map3k1SrfNgfArrb1Tgfb1Ppp3r2Mapk12Rasgrp4Nf1Sap1aNfkb1IkbkbEgfMosMap3k7ip1Mapk6EcsitNr4a1Mapkapk5PdgfbPpm1bPpp3r1nfat2/4Map4k3Ppp3cbPtpn5Ptpn5MycNtrk1Casp1Mapk8Mapk14Ppp3caMap2k6Map3k4Rac2Rasa2Dusp5B230120H23RikSos2Ppm1aGrb2Map3k5Cdc25bMap2k7mnk1/2msk1/2Hspb2Stmn1Hspb1Mapk7Pla2g10Tgfb2Raf1Mapk9Map3k7KrasMap3k14Rasgrp1sap1aIl1bAcvr1cMapkapk2Rasgrf2Tgfbr1mkk3BrafPrkcdAtf4Mapk13Il1r1NlkMapk3Casp8Atf2MaptMap3k6Elk1PtprrPak1NrasMap2k4PrkchGckDusp6Il1r2Map3k11TnfPpp3ccMapk10Map2k5Hspa1aFgf4


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. Source: KEGG


GenMAPP remarks 
Converted to human by
This pathway was inferred from Homo sapiens pathway WP382(r28779) with a 91% conversion rate.

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Ontology Terms



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  1. Zhu X, Lee HG, Raina AK, Perry G, Smith MA; ''The role of mitogen-activated protein kinase pathways in Alzheimer's disease.''; Neurosignals, 2002 PubMed Europe PMC Scholia
  2. Abell AN, Granger DA, Johnson GL; ''MEKK4 stimulation of p38 and JNK activity is negatively regulated by GSK3beta.''; J Biol Chem, 2007 PubMed Europe PMC Scholia
  3. Huang EJ, Reichardt LF; ''Trk receptors: roles in neuronal signal transduction.''; Annu Rev Biochem, 2003 PubMed Europe PMC Scholia
  4. Yang SH, Sharrocks AD, Whitmarsh AJ; ''Transcriptional regulation by the MAP kinase signaling cascades.''; Gene, 2003 PubMed Europe PMC Scholia
  5. Thévenin AF, Zony CL, Bahnson BJ, Colman RF; ''GST pi modulates JNK activity through a direct interaction with JNK substrate, ATF2.''; Protein Sci, 2011 PubMed Europe PMC Scholia
  6. Tanoue T, Nishida E; ''Docking interactions in the mitogen-activated protein kinase cascades.''; Pharmacol Ther, 2002 PubMed Europe PMC Scholia
  7. Harper SJ, LoGrasso P; ''Signalling for survival and death in neurones: the role of stress-activated kinases, JNK and p38.''; Cell Signal, 2001 PubMed Europe PMC Scholia
  8. Garcia-Guzman M, Dolfi F, Zeh K, Vuori K; ''Met-induced JNK activation is mediated by the adapter protein Crk and correlates with the Gab1 - Crk signaling complex formation.''; Oncogene, 1999 PubMed Europe PMC Scholia
  9. Cho H, Lee J, Kwak NJ, Lee KH, Rha S, Kim YH, Cho YY, Yang KH, Kim K, Lim Y; ''Silica induces nuclear factor-kappaB activation through TAK1 and NIK in Rat2 cell line.''; Toxicol Lett, 2003 PubMed Europe PMC Scholia
  10. Dent P, Yacoub A, Fisher PB, Hagan MP, Grant S; ''MAPK pathways in radiation responses.''; Oncogene, 2003 PubMed Europe PMC Scholia
  11. Takeda K, Ichijo H; ''Neuronal p38 MAPK signalling: an emerging regulator of cell fate and function in the nervous system.''; Genes Cells, 2002 PubMed Europe PMC Scholia
  12. Chen Z, Gibson TB, Robinson F, Silvestro L, Pearson G, Xu B, Wright A, Vanderbilt C, Cobb MH; ''MAP kinases.''; Chem Rev, 2001 PubMed Europe PMC Scholia


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117912view10:32, 23 May 2021EweitzModified title
114036view15:58, 17 December 2020DeSlConverted some PW names to PW nodes, minor graphical updates.
114032view15:50, 17 December 2020DeSlAdded 2 lit refs from WP3284
106898view13:37, 17 September 2019MaintBotHMDB identifier normalization
78412view10:25, 7 January 2015MaintBotadded missing graphIds
71754view20:20, 17 October 2013MaintBotAutomated update of data sources
69805view14:24, 11 July 2013Mkutmonfixing unconnected lines
69804view14:22, 11 July 2013MkutmonPeriodical save, work in progress
69803view14:21, 11 July 2013Mkutmonfixing lines (work in progress)
69799view14:14, 11 July 2013Mkutmonfixing lines (work in progress)
69198view18:23, 8 July 2013MaintBotUpdated to 2013 gpml schema
67444view11:02, 26 June 2013DdiglesOntology Term : 'mitogen activated protein kinase signaling pathway' added !
47770view05:30, 6 April 2012Khanspersupdated xref
41389view00:29, 2 March 2011MaintBotRemoved redundant pathway information and comments
35660view22:10, 12 February 2010KhanspersComment
35659view22:08, 12 February 2010KhanspersSaved comment
35658view22:06, 12 February 2010KhanspersAdded description and literature references
32980view23:33, 29 September 2009MaintBotadded xrefs
32447view17:20, 15 August 2009MaintBotFixed text labels
32121view13:52, 14 August 2009MaintBotFixed group labels
31466view21:17, 13 August 2009MaintBotFixed text labels
30838view00:03, 30 July 2009MaintBotConverted from Homo sapiens
21716view11:32, 14 November 2008MaintBot[[Pathway:Mus musculus:MAPK signaling pathway KEGG]] moved to [[Pathway:WP493]]: Moved to stable identifier
8250view13:46, 7 January 2008MaintBot[[Pathway:Mouse:MAPK signaling pathway KEGG]] moved to [[Pathway:Mus musculus:MAPK signaling pathway KEGG]]: Renaming species
7745view16:14, 18 December 2007MaintBotfixed category names
7278view12:41, 4 November 2007MaintBotAdded categories to GPML
6474view22:19, 22 May 2007S.Burelgpml file for [[Mouse:MAPK_signaling_pathway_KEGG]]

External references


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NameTypeDatabase referenceComment
Acvr1bGeneProduct11479 (Entrez Gene)
Acvr1cGeneProduct269275 (Entrez Gene)
Akt1GeneProduct11651 (Entrez Gene)
Akt2GeneProduct11652 (Entrez Gene)
Akt3GeneProduct23797 (Entrez Gene)
Arrb1GeneProduct109689 (Entrez Gene)
Arrb2GeneProduct216869 (Entrez Gene)
Atf2GeneProduct11909 (Entrez Gene)
Atf4GeneProduct11911 (Entrez Gene)
B230120H23RikGeneProduct65964 (Entrez Gene)
BdnfGeneProduct12064 (Entrez Gene)
BrafGeneProduct109880 (Entrez Gene)
Casp1GeneProduct12362 (Entrez Gene)
Casp2GeneProduct12366 (Entrez Gene)
Casp3GeneProduct12367 (Entrez Gene)
Casp6GeneProduct12368 (Entrez Gene)
Casp7GeneProduct12369 (Entrez Gene)
Casp8GeneProduct12370 (Entrez Gene)
Casp9GeneProduct12371 (Entrez Gene)
Cd14GeneProduct12475 (Entrez Gene)
Cdc25bGeneProduct12531 (Entrez Gene)
Cdc42GeneProduct12540 (Entrez Gene)
Classical MAP kinase PathwayPathway
CrkGeneProduct12928 (Entrez Gene)
CrklGeneProduct12929 (Entrez Gene)
DaxxGeneProduct13163 (Entrez Gene)
Ddit3GeneProduct13198 (Entrez Gene)
Dusp10GeneProduct63953 (Entrez Gene)
Dusp1GeneProduct19252 (Entrez Gene)
Dusp4GeneProduct319520 (Entrez Gene)
Dusp5GeneProduct240672 (Entrez Gene)
Dusp6GeneProduct67603 (Entrez Gene)
Dusp7GeneProduct235584 (Entrez Gene)
ERK5 pathwayPathway
EcsitGeneProduct26940 (Entrez Gene)
EgfGeneProduct13645 (Entrez Gene)
EgfrGeneProduct13649 (Entrez Gene)
Elk1GeneProduct13712 (Entrez Gene)
FasGeneProduct14102 (Entrez Gene)
FaslGeneProduct14103 (Entrez Gene)
Fgf4GeneProduct14175 (Entrez Gene)
FlnaGeneProduct192176 (Entrez Gene)
FosGeneProduct14281 (Entrez Gene)
Gadd45aGeneProduct13197 (Entrez Gene)
GckGeneProduct103988 (Entrez Gene)
Gna12GeneProduct14673 (Entrez Gene)
Grb2GeneProduct14784 (Entrez Gene)
Hspa1aGeneProduct193740 (Entrez Gene)
Hspa5GeneProduct14828 (Entrez Gene)
Hspa8GeneProduct15481 (Entrez Gene)
Hspb1GeneProduct15507 (Entrez Gene)
Hspb2GeneProduct69253 (Entrez Gene)
IkbkbGeneProduct16150 (Entrez Gene)
IkbkgGeneProduct16151 (Entrez Gene)
Il1aGeneProduct16175 (Entrez Gene)
Il1bGeneProduct16176 (Entrez Gene)
Il1r1GeneProduct16177 (Entrez Gene)
Il1r2GeneProduct16178 (Entrez Gene)
JNK & p38 MAP kinase pathwayPathway
JunGeneProduct16476 (Entrez Gene)
JundGeneProduct16478 (Entrez Gene)
KrasGeneProduct16653 (Entrez Gene)
Map2k1GeneProduct26395 (Entrez Gene)
Map2k2GeneProduct26396 (Entrez Gene)
Map2k4GeneProduct26398 (Entrez Gene)
Map2k5GeneProduct23938 (Entrez Gene)
Map2k6GeneProduct26399 (Entrez Gene)
Map2k7GeneProduct26400 (Entrez Gene)
Map3k11GeneProduct26403 (Entrez Gene)
Map3k12GeneProduct26404 (Entrez Gene)
Map3k1GeneProduct26401 (Entrez Gene)
Map3k13GeneProduct71751 (Entrez Gene)
Map3k14GeneProduct53859 (Entrez Gene)
Map3k4GeneProduct26407 (Entrez Gene)
Map3k5GeneProduct26408 (Entrez Gene)
Map3k6GeneProduct53608 (Entrez Gene)
Map3k7GeneProduct26409 (Entrez Gene)
Map3k7ip1GeneProduct66513 (Entrez Gene)
Map3k7ip2GeneProduct68652 (Entrez Gene)
Map3k8GeneProduct26410 (Entrez Gene)
Map4k1GeneProduct26411 (Entrez Gene)
Map4k3GeneProduct225028 (Entrez Gene)
Map4k4GeneProduct26921 (Entrez Gene)
Mapk10GeneProduct26414 (Entrez Gene)
Mapk12GeneProduct29857 (Entrez Gene)
Mapk1GeneProduct26413 (Entrez Gene)
Mapk13GeneProduct26415 (Entrez Gene)
Mapk14GeneProduct26416 (Entrez Gene)
Mapk3GeneProduct26417 (Entrez Gene)
Mapk4GeneProduct225724 (Entrez Gene)
Mapk6GeneProduct50772 (Entrez Gene)
Mapk7GeneProduct23939 (Entrez Gene)
Mapk8GeneProduct26419 (Entrez Gene)
Mapk8ip3GeneProduct30957 (Entrez Gene)
Mapk9GeneProduct26420 (Entrez Gene)
Mapkapk2GeneProduct17164 (Entrez Gene)
Mapkapk5GeneProduct17165 (Entrez Gene)
MaptGeneProduct17762 (Entrez Gene)
MaxGeneProduct17187 (Entrez Gene)
Mef2cGeneProduct17260 (Entrez Gene)
Mink1GeneProduct50932 (Entrez Gene)
MosGeneProduct17451 (Entrez Gene)
MrasGeneProduct17532 (Entrez Gene)
MycGeneProduct17869 (Entrez Gene)
Nf1GeneProduct18015 (Entrez Gene)
Nfkb1GeneProduct18033 (Entrez Gene)
NgfGeneProduct18049 (Entrez Gene)
NlkGeneProduct18099 (Entrez Gene)
Nr4a1GeneProduct15370 (Entrez Gene)
NrasGeneProduct18176 (Entrez Gene)
Ntf5GeneProduct78405 (Entrez Gene)
Ntrk1GeneProduct18211 (Entrez Gene)
Pak1GeneProduct18479 (Entrez Gene)
Pak2GeneProduct224105 (Entrez Gene)
PdgfbGeneProduct18591 (Entrez Gene)
PdgfrbGeneProduct18596 (Entrez Gene)
Pla2g10GeneProduct26565 (Entrez Gene)
Pla2g5GeneProduct18784 (Entrez Gene)
Ppm1aGeneProduct19042 (Entrez Gene)
Ppm1bGeneProduct19043 (Entrez Gene)
Ppp3caGeneProduct19055 (Entrez Gene)
Ppp3cbGeneProduct19056 (Entrez Gene)
Ppp3ccGeneProduct19057 (Entrez Gene)
Ppp3r1GeneProduct19058 (Entrez Gene)
Ppp3r2GeneProduct19059 (Entrez Gene)
Ppp5cGeneProduct19060 (Entrez Gene)
PrkacaGeneProduct18747 (Entrez Gene)
PrkcbGeneProduct18751 (Entrez Gene)
PrkccGeneProduct18752 (Entrez Gene)
PrkcdGeneProduct18753 (Entrez Gene)
PrkchGeneProduct18755 (Entrez Gene)
PrkczGeneProduct18762 (Entrez Gene)
Ptpn5GeneProduct19259 (Entrez Gene)
Ptpn7GeneProduct320139 (Entrez Gene)
PtprrGeneProduct19279 (Entrez Gene)
Rac1GeneProduct19353 (Entrez Gene)
Rac2GeneProduct19354 (Entrez Gene)
Raf1GeneProduct110157 (Entrez Gene)
Rap1aGeneProduct109905 (Entrez Gene)
Rap1bGeneProduct215449 (Entrez Gene)
Rasa1GeneProduct218397 (Entrez Gene)
Rasa2GeneProduct114713 (Entrez Gene)
Rasgrf2GeneProduct19418 (Entrez Gene)
Rasgrp1GeneProduct19419 (Entrez Gene)
Rasgrp4GeneProduct233046 (Entrez Gene)
Rps6ka3GeneProduct110651 (Entrez Gene)
Sos2GeneProduct20663 (Entrez Gene)
SrfGeneProduct20807 (Entrez Gene)
Stk3GeneProduct56274 (Entrez Gene)
Stmn1GeneProduct16765 (Entrez Gene)
Taok1GeneProduct216965 (Entrez Gene)
Taok2GeneProductMGI:1915919 (MGI)
Tgfb1GeneProduct21803 (Entrez Gene)
Tgfb2GeneProduct21808 (Entrez Gene)
Tgfb3GeneProduct21809 (Entrez Gene)
Tgfbr1GeneProduct21812 (Entrez Gene)
Tgfbr2GeneProduct21813 (Entrez Gene)
Tmem37GeneProduct170706 (Entrez Gene)
TnfGeneProduct21926 (Entrez Gene)
Traf2GeneProduct22030 (Entrez Gene)
Traf6GeneProduct22034 (Entrez Gene)
Trp53GeneProduct22059 (Entrez Gene)
cAMPMetaboliteHMDB0000058 (HMDB)

Annotated Interactions

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