MAPK Signaling Pathway (Rattus norvegicus)

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2-101DNAHeteromeric G-proteinp38CellPhosphatidylinositolsignaling systemJNKMAPKKKKClassical MAP kinase PathwayERK5 pathwayCa2+Transcription factorsPTPIP3Proliferation, differentiationProliferation, inflammation, anti-apoptosisMAPKKKp53 signaling pathwayProliferation, differentiation,inflammationJNK & p38 MAP kinase pathwayDNAWnt signaling pathwayMAPKDNAMAPKKLPSMKPPTPDNASerum, EGF,reactive oxygen species.or Srk tyrokinase downstreamProliferation, differentiationCycleSerum, cytotoxic drugs, irradiation,heatshock, reactive oxy speciesLPS and other stressDAGApoptosisDNADNA damageTraf6Pla2g10SOS2Acvr1bHspb1PrkczTgfb2Mapk8ip3Cdc25bEcsitRps6ka3Tgfb1Rac2PTPN5Ppp3ccCasp6Mapk3FlnaMef2cPpp5cHspa5mkk3Casp1Il1r1Map2k6MAPTDusp6HSPA1AFgf4Nf1MAPK7LOC303259Dusp4Il1r2Ppp3r2Rasgrf2Arrb2Map2k7Nfkb1Cd14nfat2/4Arrb1Tgfbr2Map2k1FaslgSap1aPpp3r1CrkAkt2PrkcdPpp3cbMap3k12Ntrk1Mapk8FosTp53Map3k7PrkcdAtf4Tgfbr1IkbkgCasp2PdgfrbMap3k4Rap1bMap2k1ip1Rap1aCrklDusp10Map3k8CDC42NgfEgfrElk1PrkacaNrasMap2k2Rasgrp4ZAKPak2Stmn1Casp9Rasgrp1MaxKrasMap3k14Hspb2TnfPtprrMapk6Stk3IkbkbEgfmsk1/2MAP3K7IP1sap1aRasa2PTPN5BrafPtpn7Tmem37Dusp5Il1aTraf2PrkcbPpp3caGadd45aGstt2Casp3Map3k6Atf2Il1bPdgfbfgfrLOC303823Ppm1aMap4k1Map2k4SrfTAOK2GckMrasMapk4Grb2Mapk10Mapk13Akt3Ptpn7MAP3K5Ddit3Casp8cAMPBdnfPak1Rac1FasRaf1MEKK2/3Taok1PtprrPpm1bGna12MosMap4k3mnk1/2Mapk9Mapkapk2Atf4Dusp7PrkcgCasp7Mapk14Mapk12Dusp1Mapkapk5Hspa8Tgfb3JunNlkMycMap3k11Mapk1Nr4a1Map3k7ip2Rasa1JundDaxxMap2k5Map3k1MAP4K4Ntf4Akt1PrkchPla2g5Acvr1c


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 88% conversion rate.

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  1. Yang SH, Sharrocks AD, Whitmarsh AJ; ''Transcriptional regulation by the MAP kinase signaling cascades.''; Gene, 2003 PubMed Europe PMC Scholia
  2. Huang EJ, Reichardt LF; ''Trk receptors: roles in neuronal signal transduction.''; Annu Rev Biochem, 2003 PubMed Europe PMC Scholia
  3. 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
  4. 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
  5. Dent P, Yacoub A, Fisher PB, Hagan MP, Grant S; ''MAPK pathways in radiation responses.''; Oncogene, 2003 PubMed Europe PMC Scholia
  6. 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
  7. Tanoue T, Nishida E; ''Docking interactions in the mitogen-activated protein kinase cascades.''; Pharmacol Ther, 2002 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. 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
  11. Chen CY, Weng YH, Chien KY, Lin KJ, Yeh TH, Cheng YP, Lu CS, Wang HL; ''(G2019S) LRRK2 activates MKK4-JNK pathway and causes degeneration of SN dopaminergic neurons in a transgenic mouse model of PD.''; Cell Death Differ, 2012 PubMed Europe PMC Scholia


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106982view13:44, 17 September 2019MaintBotHMDB identifier normalization
105688view20:58, 13 August 2019Khanspersremoved human-specific drug targeting and mutation
96398view10:11, 12 March 2018EgonwReplaced secondary ChEBI identifiers with primary identifiers.
95780view14:33, 19 January 2018MkutmonHomology conversion update
95213view12:05, 24 November 2017Mkutmonadded homology converter comment source
83027view01:58, 18 November 2015MkutmonFix outdated identifiers
69374view18:55, 8 July 2013MaintBotUpdated to 2013 gpml schema
67442view11:02, 26 June 2013DdiglesOntology Term : 'mitogen activated protein kinase signaling pathway' added !
47771view05:31, 6 April 2012Khanspersupdated xref
41688view02:36, 2 March 2011MaintBotRemoved redundant pathway information and comments
35661view22:13, 12 February 2010KhanspersAdded Description and LIt Refs
34074view19:11, 9 December 2009MaintBotAutomatic update of empty xrefs
32409view17:04, 15 August 2009MaintBotFixed text labels
32065view13:35, 14 August 2009MaintBotFixed group labels
31440view21:05, 13 August 2009MaintBotFixed text labels
30944view00:41, 30 July 2009MaintBotConverted from Homo sapiens
21429view11:31, 14 November 2008MaintBot[[Pathway:Rattus norvegicus:MAPK signaling pathway KEGG]] moved to [[Pathway:WP358]]: Moved to stable identifier
8252view13:46, 7 January 2008MaintBot[[Pathway:Rat:MAPK signaling pathway KEGG]] moved to [[Pathway:Rattus norvegicus:MAPK signaling pathway KEGG]]: Renaming species
7746view16:15, 18 December 2007MaintBotfixed category names
7279view12:41, 4 November 2007MaintBotAdded categories to GPML
6574view22:20, 22 May 2007S.Burelgpml file for [[Rat:MAPK_signaling_pathway_ KEGG]]

External references


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NameTypeDatabase referenceComment
Acvr1bGeneProduct29381 (Entrez Gene)
Acvr1cGeneProduct245921 (Entrez Gene)
Akt1GeneProduct24185 (Entrez Gene)
Akt2GeneProduct25233 (Entrez Gene)
Akt3GeneProduct29414 (Entrez Gene)
Arrb1GeneProduct25387 (Entrez Gene)
Arrb2GeneProduct25388 (Entrez Gene)
Atf2GeneProduct81647 (Entrez Gene)
Atf4GeneProduct79255 (Entrez Gene)
BdnfGeneProduct24225 (Entrez Gene)
BrafGeneProduct114486 (Entrez Gene)
CDC42GeneProduct64465 (Entrez Gene)
Casp1GeneProduct25166 (Entrez Gene)
Casp2GeneProduct64314 (Entrez Gene)
Casp3GeneProduct25402 (Entrez Gene)
Casp6GeneProduct83584 (Entrez Gene)
Casp7GeneProduct64026 (Entrez Gene)
Casp8GeneProduct64044 (Entrez Gene)
Casp9GeneProduct58918 (Entrez Gene)
Cd14GeneProduct60350 (Entrez Gene)
Cdc25bGeneProduct171103 (Entrez Gene)
CrkGeneProduct54245 (Entrez Gene)
CrklGeneProduct287942 (Entrez Gene)
DaxxGeneProduct140926 (Entrez Gene)
Ddit3GeneProduct29467 (Entrez Gene)
Dusp10GeneProduct63995 (Entrez Gene)
Dusp1GeneProduct114856 (Entrez Gene)
Dusp4GeneProduct60587 (Entrez Gene)
Dusp5GeneProduct171109 (Entrez Gene)
Dusp6GeneProduct116663 (Entrez Gene)
Dusp7GeneProduct300980 (Entrez Gene)
EcsitGeneProduct300447 (Entrez Gene)
EgfGeneProduct25313 (Entrez Gene)
EgfrGeneProduct24329 (Entrez Gene)
Elk1GeneProduct314436 (Entrez Gene)
FasGeneProduct246097 (Entrez Gene)
FaslgGeneProduct25385 (Entrez Gene)
Fgf4GeneProduct116499 (Entrez Gene)
FlnaGeneProduct293860 (Entrez Gene)
FosGeneProduct314322 (Entrez Gene)
Gadd45aGeneProduct25112 (Entrez Gene)
GckGeneProduct24385 (Entrez Gene)
Gna12GeneProduct81663 (Entrez Gene)
Grb2GeneProduct81504 (Entrez Gene)
Gstt2GeneProduct29487 (Entrez Gene)
HSPA1AGeneProduct24472 (Entrez Gene)
Hspa5GeneProduct25617 (Entrez Gene)
Hspa8GeneProduct24468 (Entrez Gene)
Hspb1GeneProduct24471 (Entrez Gene)
Hspb2GeneProduct161476 (Entrez Gene)
IkbkbGeneProduct84351 (Entrez Gene)
IkbkgGeneProduct309295 (Entrez Gene)
Il1aGeneProduct24493 (Entrez Gene)
Il1bGeneProduct24494 (Entrez Gene)
Il1r1GeneProduct25663 (Entrez Gene)
Il1r2GeneProduct117022 (Entrez Gene)
JunGeneProduct24516 (Entrez Gene)
JundGeneProduct24518 (Entrez Gene)
KrasGeneProduct24525 (Entrez Gene)
LOC303259GeneProduct303259 (Entrez Gene)
LOC303823GeneProduct303823 (Entrez Gene)
MAP3K5GeneProduct293015 (Entrez Gene)
MAP3K7IP1GeneProduct315139 (Entrez Gene)
MAP4K4GeneProduct301363 (Entrez Gene)
MAPK7GeneProduct114509 (Entrez Gene)
MAPTGeneProduct29477 (Entrez Gene)
Map2k1GeneProduct170851 (Entrez Gene)
Map2k1ip1GeneProduct362045 (Entrez Gene)
Map2k2GeneProduct58960 (Entrez Gene)
Map2k4GeneProduct287398 (Entrez Gene)
Map2k5GeneProduct29568 (Entrez Gene)
Map2k6GeneProduct114495 (Entrez Gene)
Map2k7GeneProduct363855 (Entrez Gene)
Map3k1GeneProduct116667 (Entrez Gene)
Map3k11GeneProduct309168 (Entrez Gene)
Map3k12GeneProduct25579 (Entrez Gene)
Map3k14GeneProduct360640 (Entrez Gene)
Map3k4GeneProduct308106 (Entrez Gene)
Map3k6GeneProduct313022 (Entrez Gene)
Map3k7GeneProduct313121 (Entrez Gene)
Map3k7ip2GeneProduct308267 (Entrez Gene)
Map3k8GeneProduct116596 (Entrez Gene)
Map4k1GeneProduct292763 (Entrez Gene)
Map4k3GeneProduct170920 (Entrez Gene)
Mapk10GeneProduct25272 (Entrez Gene)
Mapk1GeneProduct116590 (Entrez Gene)
Mapk12GeneProduct60352 (Entrez Gene)
Mapk13GeneProduct29513 (Entrez Gene)
Mapk14GeneProduct81649 (Entrez Gene)
Mapk3GeneProduct50689 (Entrez Gene)
Mapk4GeneProduct54268 (Entrez Gene)
Mapk6GeneProduct58840 (Entrez Gene)
Mapk8GeneProduct116554 (Entrez Gene)
Mapk8ip3GeneProduct302983 (Entrez Gene)
Mapk9GeneProduct50658 (Entrez Gene)
Mapkapk2GeneProduct289014 (Entrez Gene)
Mapkapk5GeneProduct498183 (Entrez Gene)
MaxGeneProduct60661 (Entrez Gene)
Mef2cGeneProduct499497 (Entrez Gene)
MosGeneProduct24559 (Entrez Gene)
MrasGeneProduct25482 (Entrez Gene)
MycGeneProduct24577 (Entrez Gene)
Nf1GeneProduct24592 (Entrez Gene)
Nfkb1GeneProduct81736 (Entrez Gene)
NgfGeneProduct310738 (Entrez Gene)
NlkGeneProduct497961 (Entrez Gene)
Nr4a1GeneProduct79240 (Entrez Gene)
NrasGeneProduct24605 (Entrez Gene)
Ntf4GeneProduct25730 (Entrez Gene)
Ntrk1GeneProduct59109 (Entrez Gene)
PTPN5GeneProduct29644 (Entrez Gene)
Pak1GeneProduct29431 (Entrez Gene)
Pak2GeneProduct29432 (Entrez Gene)
PdgfbGeneProduct24628 (Entrez Gene)
PdgfrbGeneProduct24629 (Entrez Gene)
Pla2g10GeneProduct29359 (Entrez Gene)
Pla2g5GeneProduct29354 (Entrez Gene)
Ppm1aGeneProduct24666 (Entrez Gene)
Ppm1bGeneProduct24667 (Entrez Gene)
Ppp3caGeneProduct24674 (Entrez Gene)
Ppp3cbGeneProduct24675 (Entrez Gene)
Ppp3ccGeneProduct171378 (Entrez Gene)
Ppp3r1GeneProduct29748 (Entrez Gene)
Ppp3r2GeneProduct29749 (Entrez Gene)
Ppp5cGeneProduct65179 (Entrez Gene)
PrkacaGeneProduct25636 (Entrez Gene)
PrkcbGeneProduct25023 (Entrez Gene)
PrkcdGeneProduct170538 (Entrez Gene)
PrkcgGeneProduct24681 (Entrez Gene)
PrkchGeneProduct81749 (Entrez Gene)
PrkczGeneProduct25522 (Entrez Gene)
Ptpn7GeneProduct246781 (Entrez Gene)
PtprrGeneProduct94202 (Entrez Gene)
Rac1GeneProduct363875 (Entrez Gene)
Rac2GeneProduct366957 (Entrez Gene)
Raf1GeneProduct24703 (Entrez Gene)
Rap1aGeneProduct295347 (Entrez Gene)
Rap1bGeneProduct171337 (Entrez Gene)
Rasa1GeneProduct25676 (Entrez Gene)
Rasa2GeneProduct25597 (Entrez Gene)
Rasgrf2GeneProduct114513 (Entrez Gene)
Rasgrp1GeneProduct29434 (Entrez Gene)
Rasgrp4GeneProduct170668 (Entrez Gene)
Rps6ka3GeneProduct501560 (Entrez Gene)
SOS2GeneProduct85384 (Entrez Gene)
SrfGeneProduct501099 (Entrez Gene)
Stk3GeneProduct65189 (Entrez Gene)
Stmn1GeneProduct29332 (Entrez Gene)
TAOK2GeneProduct64666 (Entrez Gene)
Taok1GeneProduct286993 (Entrez Gene)
Tgfb1GeneProduct59086 (Entrez Gene)
Tgfb2GeneProduct81809 (Entrez Gene)
Tgfb3GeneProduct25717 (Entrez Gene)
Tgfbr1GeneProduct29591 (Entrez Gene)
Tgfbr2GeneProduct81810 (Entrez Gene)
Tmem37GeneProduct245953 (Entrez Gene)
TnfGeneProduct24835 (Entrez Gene)
Tp53GeneProduct24842 (Entrez Gene)
Traf2GeneProduct311786 (Entrez Gene)
Traf6GeneProduct311245 (Entrez Gene)
cAMPMetaboliteHMDB00058 (HMDB)

Annotated Interactions

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