MAPK signaling pathway (Mus musculus)

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1-7, 9-12DNAProliferation, differentiationClassical MAP kinase PathwayPTPSerum,cytotoxic drugs, irradiation,heatshock, ROS, LPS and otherSerum, EGF,reactive oxygen species.or Srk tyrokinase downstreamDNAProliferation, differentiationMAPKKMAPKTranscription factorsMKPProliferation, inflammation, anti-apoptosisp38LPSMAPKKKKMAPKKKDNAJNK & p38 MAP kinase 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, differentiation, apoptosisProliferation, differentiation, apoptosisP53 signaling pathwayGstt2Gstt3Gstm1Gstm2Gstm3Gstm4Gstt4Gstp1Gsta1Gsta2Gsta3Gsta4Hspa1bwnt:signaling pathwayErk5 pathwayGSTHSPPPP3CMKPCasp3Cyp2f2Cyp2e1Cyp2d22Cyp2c44


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


This pathway was inferred from Homo sapiens pathway WP382(r28779) with a 91% conversion rate.

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  1. Tanoue T, Nishida E; ''Docking interactions in the mitogen-activated protein kinase cascades.''; Pharmacol Ther, 2002 PubMed Europe PMC Scholia
  2. 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
  3. 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
  4. Huang EJ, Reichardt LF; ''Trk receptors: roles in neuronal signal transduction.''; Annu Rev Biochem, 2003 PubMed Europe PMC Scholia
  5. 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
  6. Thévenin AF1, 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
  7. Garcia-Guzman M1, 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.''; , 1999 PubMed Europe PMC Scholia
  8. 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
  9. 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
  10. 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
  11. Yang SH, Sharrocks AD, Whitmarsh AJ; ''Transcriptional regulation by the MAP kinase signaling cascades.''; Gene, 2003 PubMed Europe PMC Scholia
  12. Dent P, Yacoub A, Fisher PB, Hagan MP, Grant S; ''MAPK pathways in radiation responses.''; Oncogene, 2003 PubMed Europe PMC Scholia


109369view14:38, 16 March 2020L DupuisConverted interaction lines representing cell membrane to graphical lines
92697view19:27, 28 June 2017Mkutmonfix invalid xref
87397view11:05, 22 July 2016MaintBotadded missing graphids
80951view17:47, 1 July 2015ZganNew pathway

External references


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NameTypeDatabase referenceComment
Acvr1bGeneProduct11479 (Entrez Gene)
Acvr1cGeneProduct269275 (Entrez Gene)
Akt1GeneProduct11651 (Entrez Gene)
Akt2GeneProduct11652 (Entrez Gene)
Akt3GeneProduct23797 (Entrez Gene)
Atf2GeneProduct11909 (Entrez Gene)
Atf4GeneProduct11911 (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)
CrkGeneProduct12928 (Entrez Gene)
CrklGeneProduct12929 (Entrez Gene)
Cyp2c44GeneProduct226143 (Entrez Gene)
Cyp2d22GeneProduct56448 (Entrez Gene)
Cyp2e1GeneProduct13106 (Entrez Gene)
Cyp2f2GeneProduct13107 (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)
EgfGeneProduct13645 (Entrez Gene)
EgfrGeneProduct13649 (Entrez Gene)
Elk1GeneProduct13712 (Entrez Gene)
FasGeneProduct14102 (Entrez Gene)
FaslGeneProduct14103 (Entrez Gene)
Fgf4GeneProduct14175 (Entrez Gene)
Gna12GeneProduct14673 (Entrez Gene)
Grb2GeneProduct14784 (Entrez Gene)
Gsta1GeneProduct14857 (Entrez Gene)
Gsta2GeneProduct14858 (Entrez Gene)
Gsta3GeneProduct14859 (Entrez Gene)
Gsta4GeneProduct14860 (Entrez Gene)
Gstm1GeneProduct14862 (Entrez Gene)
Gstm2GeneProduct14863 (Entrez Gene)
Gstm3GeneProduct14864 (Entrez Gene)
Gstm4GeneProduct14865 (Entrez Gene)
Gstp1GeneProduct14870 (Entrez Gene)
Gstt1GeneProduct14871 (Entrez Gene)
Gstt2GeneProduct14872 (Entrez Gene)
Gstt3GeneProduct103140 (Entrez Gene)
Gstt4GeneProduct75886 (Entrez Gene)
Hspa1aGeneProduct193740 (Entrez Gene)
Hspa1bGeneProduct15511 (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)
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)
Map3k2GeneProduct26405 (Entrez Gene)
Map3k3GeneProduct26406 (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)
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)
Rasgrf2GeneProductENSMUSG00000021708 (Ensembl)
Rasgrp1GeneProduct19419 (Entrez Gene)
Rasgrp4GeneProduct233046 (Entrez Gene)
Rps6ka3GeneProduct110651 (Entrez Gene)
Sos2GeneProduct20663 (Entrez Gene)
SrfGeneProduct20807 (Entrez Gene)
Stmn1GeneProduct16765 (Entrez Gene)
Tab1GeneProduct66513 (Entrez Gene)
Tab2GeneProduct68652 (Entrez Gene)
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)
ZakGeneProduct65964 (Entrez Gene)

Annotated Interactions

No annotated interactions
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