PATHWAY: ko04010 Help
Entry Name MAPK signaling pathway
Description 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.
Class Environmental Information Processing; Signal transductionBRITE hierarchy
Pathway map Other DBs Orthology K02308 DAXX; death-associated protein 6
K02580 NFKB1; nuclear factor NF-kappa-B p105 subunit
K02582 NGFB; nerve growth factor, beta
K02583 NGFR, TNFRSF16, CD271; tumor necrosis factor receptor superfamily member 16
K03156 TNF, TNFA; tumor necrosis factor superfamily, member 2
K03158 TNFRSF1A, TNFR1, CD120a; tumor necrosis factor receptor superfamily member 1A
K03171 TRADD; tumor necrosis factor receptor type 1-associated DEATH domain protein
K03176 NTRK1, TRKA; neurotrophic tyrosine kinase receptor type 1 [EC:2.7.10.1 ]
K03283 HSPA1_6_8; heat shock 70kDa protein 1/6/8
K04344 CACNA1A, CAV2.1; voltage-dependent calcium channel P/Q type alpha-1A
K04346 GNA12; guanine nucleotide-binding protein subunit alpha-12
K04347 GNG12; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-12
K04348 PPP3C, CNA; serine/threonine-protein phosphatase 2B catalytic subunit [EC:3.1.3.16 ]
K04349 RASGRF1; Ras-specific guanine nucleotide-releasing factor 1
K04350 RASGRP1; RAS guanyl-releasing protein 1
K04352 RASA1, RASGAP; Ras GTPase-activating protein 1
K04353 RAP1A; Ras-related protein Rap-1A
K04355 BDNF; brain-derived neurotrophic factor
K04357 EGF; epidermal growth factor
K04358 FGF; fibroblast growth factor
K04359 PDGFA; platelet-derived growth factor subunit A
K04360 NTRK2, TRKB; neurotrophic tyrosine kinase receptor type 2 [EC:2.7.10.1 ]
K04362 FGFR1, CD331; fibroblast growth factor receptor 1 [EC:2.7.10.1 ]
K04363 PDGFRA, CD140A; platelet-derived growth factor receptor alpha [EC:2.7.10.1 ]
K04364 GRB2; growth factor receptor-bound protein 2
K04365 BRAF; B-Raf proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1 ]
K04366 RAF1; RAF proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1 ]
K04368 MAP2K1, MEK1; mitogen-activated protein kinase kinase 1 [EC:2.7.12.2 ]
K04369 MAP2K2, MEK2; mitogen-activated protein kinase kinase 2 [EC:2.7.12.2 ]
K04370 LAMTOR3, MP1, MAP2K1IP1; ragulator complex protein LAMTOR3
K04372 MKNK, MNK; MAP kinase interacting serine/threonine kinase [EC:2.7.11.1 ]
K04373 RPS6KA; ribosomal protein S6 kinase alpha-1/2/3/6 [EC:2.7.11.1 ]
K04374 ATF4, CREB2; cyclic AMP-dependent transcription factor ATF-4
K04375 ELK1; ETS domain-containing protein Elk-1
K04376 ELK4, SAP1; ETS domain-containing protein Elk-4
K04377 MYC; Myc proto-oncogene protein
K04378 SRF; serum response factor
K04379 FOS; proto-oncogene protein c-fos
K04380 MAPT, TAU; microtubule-associated protein tau
K04383 IL1A; interleukin 1 alpha
K04386 IL1R1, CD121a; interleukin 1 receptor type I
K04389 TNFSF6, FASL, CD178; tumor necrosis factor ligand superfamily member 6
K04390 TNFRSF6, FAS, CD95; tumor necrosis factor receptor superfamily member 6
K04391 CD14; monocyte differentiation antigen CD14
K04392 RAC1; Ras-related C3 botulinum toxin substrate 1
K04393 CDC42; cell division control protein 42
K04402 GADD45; growth arrest and DNA-damage-inducible protein
K04403 MAP3K7IP1, TAB1; TAK1-binding protein 1
K04404 MAP3K7IP2, TAB2; TAK1-binding protein 2
K04405 ECSIT; evolutionarily conserved signaling intermediate in Toll pathway
K04406 MAP4K3, GLK; mitogen-activated protein kinase kinase kinase kinase 3 [EC:2.7.11.1 ]
K04407 MAP4K4, HGK; mitogen-activated protein kinase kinase kinase kinase 4 [EC:2.7.11.1 ]
K04408 MAP4K1, HPK1; mitogen-activated protein kinase kinase kinase kinase 1 [EC:2.7.11.1 ]
K04411 STK4, MST1; serine/threonine kinase 4
K04412 STK3, MST2; serine/threonine kinase 3
K04414 MAP4K2, GCK; mitogen-activated protein kinase kinase kinase kinase 2 [EC:2.7.11.1 ]
K04415 MAP3K8, COT; mitogen-activated protein kinase kinase kinase 8 [EC:2.7.11.25 ]
K04416 MAP3K1, MEKK1; mitogen-activated protein kinase kinase kinase 1 [EC:2.7.11.25 ]
K04417 MAP3K9, MLK1; mitogen-activated protein kinase kinase kinase 9 [EC:2.7.11.25 ]
K04418 MAP3K10, MLK2; mitogen-activated protein kinase kinase kinase 10 [EC:2.7.11.25 ]
K04419 MAP3K11, MLK3; mitogen-activated protein kinase kinase kinase 11 [EC:2.7.11.25 ]
K04420 MAP3K2, MEKK2; mitogen-activated protein kinase kinase kinase 2 [EC:2.7.11.25 ]
K04421 MAP3K3, MEKK3; mitogen-activated protein kinase kinase kinase 3 [EC:2.7.11.25 ]
K04422 MAP3K13, LZK; mitogen-activated protein kinase kinase kinase 13 [EC:2.7.11.25 ]
K04423 MAP3K12, MUK; mitogen-activated protein kinase kinase kinase 12 [EC:2.7.11.25 ]
K04424 ZAK, MLTK; sterile alpha motif and leucine zipper containing kinase AZK [EC:2.7.11.25 ]
K04425 MAP3K6, ASK2; mitogen-activated protein kinase kinase kinase 6 [EC:2.7.11.25 ]
K04426 MAP3K5, ASK1; mitogen-activated protein kinase kinase kinase 5 [EC:2.7.11.25 ]
K04427 MAP3K7, TAK1; mitogen-activated protein kinase kinase kinase 7 [EC:2.7.11.25 ]
K04428 MAP3K4, MEKK4; mitogen-activated protein kinase kinase kinase 4 [EC:2.7.11.25 ]
K04430 MAP2K4, MKK4; mitogen-activated protein kinase kinase 4 [EC:2.7.12.2 ]
K04431 MAP2K7, MKK7; mitogen-activated protein kinase kinase 7 [EC:2.7.12.2 ]
K04432 MAP2K3, MKK3; mitogen-activated protein kinase kinase 3 [EC:2.7.12.2 ]
K04433 MAP2K6, MKK6; mitogen-activated protein kinase kinase 6 [EC:2.7.12.2 ]
K04434 MAPK8IP1, JIP1; mitogen-activated protein kinase 8 interacting protein 1
K04435 MAPK8IP2, JIP2; mitogen-activated protein kinase 8 interacting protein 2
K04436 MAPK8IP3, JIP3; mitogen-activated protein kinase 8 interacting protein 3
K04438 CRK, CRKII; C-crk adapter molecule crk
K04440 JNK; mitogen-activated protein kinase 8/9/10 (c-Jun N-terminal kinase) [EC:2.7.11.24 ]
K04442 MAPKAPK5, PRAK; mitogen-activated protein kinase-activated protein kinase 5 [EC:2.7.11.1 ]
K04443 MAPKAPK2; mitogen-activated protein kinase-activated protein kinase 2 [EC:2.7.11.1 ]
K04444 MAPKAPK3; mitogen-activated protein kinase-activated protein kinase 3 [EC:2.7.11.1 ]
K04445 RPS6KA5, MSK1; ribosomal protein S6 kinase alpha-5 [EC:2.7.11.1 ]
K04446 NFATC1, NFAT2, NFATC; nuclear factor of activated T-cells, cytoplasmic 1
K04448 JUN; transcription factor AP-1
K04449 JUND; transcription factor jun-D
K04450 ATF2, CREBP1; cyclic AMP-dependent transcription factor ATF-2
K04451 TP53, P53; tumor protein p53
K04452 DDIT3, GADD153; DNA damage-inducible transcript 3
K04454 MEF2C; MADS-box transcription enhancer factor 2C
K04455 HSPB1; heat shock protein beta-1
K04458 PTPRR; receptor-type tyrosine-protein phosphatase R [EC:3.1.3.48 ]
K04462 MECOM, EVI1, PRDM3; [histone H3]-lysine9 N-methyltransferase (ecotropic virus integration site 1 protein) [EC:2.1.1.367 ]
K04463 MAP2K5, MEK5; mitogen-activated protein kinase kinase 5 [EC:2.7.12.2 ]
K04465 NR4A1, HMR; nuclear receptor subfamily 4 group A member 1
K04466 MAP3K14, NIK; mitogen-activated protein kinase kinase kinase 14 [EC:2.7.11.25 ]
K04467 IKBKA, IKKA, CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha [EC:2.7.11.10 ]
K04469 NFKB2; nuclear factor of kappa light polypeptide gene enhancer in B-cells 2
K04519 IL1B; interleukin 1 beta
K04723 IL1RAP; interleukin 1 receptor accessory protein
K04729 MYD88; myeloid differentiation primary response protein MyD88
K04730 IRAK1; interleukin-1 receptor-associated kinase 1 [EC:2.7.11.1 ]
K04733 IRAK4; interleukin-1 receptor-associated kinase 4 [EC:2.7.11.1 ]
K04735 RELA; transcription factor p65
K04849 CACNA1B, CAV2.2; voltage-dependent calcium channel N type alpha-1B
K04850 CACNA1C, CAV1.2; voltage-dependent calcium channel L type alpha-1C
K04851 CACNA1D, CAV1.3; voltage-dependent calcium channel L type alpha-1D
K04852 CACNA1E, CAV2.3; voltage-dependent calcium channel R type alpha-1E
K04853 CACNA1F, CAV1.4; voltage-dependent calcium channel L type alpha-1F
K04854 CACNA1G, CAV3.1; voltage-dependent calcium channel T type alpha-1G
K04855 CACNA1H, CAV3.2; voltage-dependent calcium channel T type alpha-1H
K04856 CACNA1I, CAV3.3; voltage-dependent calcium channel T type alpha-1I
K04857 CACNA1S, CAV1.1; voltage-dependent calcium channel L type alpha-1S
K04858 CACNA2D1; voltage-dependent calcium channel alpha-2/delta-1
K04859 CACNA2D2; voltage-dependent calcium channel alpha-2/delta-2
K04860 CACNA2D3; voltage-dependent calcium channel alpha-2/delta-3
K04861 CACNA2D4; voltage-dependent calcium channel alpha-2/delta-4
K04862 CACNB1; voltage-dependent calcium channel beta-1
K04863 CACNB2; voltage-dependent calcium channel beta-2
K04864 CACNB3; voltage-dependent calcium channel beta-3
K04865 CACNB4; voltage-dependent calcium channel beta-4
K04866 CACNG1; voltage-dependent calcium channel gamma-1
K04867 CACNG2; voltage-dependent calcium channel gamma-2
K04868 CACNG3; voltage-dependent calcium channel gamma-3
K04869 CACNG4; voltage-dependent calcium channel gamma-4
K04870 CACNG5; voltage-dependent calcium channel gamma-5
K04871 CACNG6; voltage-dependent calcium channel gamma-6
K04872 CACNG7; voltage-dependent calcium channel gamma-7
K04873 CACNG8; voltage-dependent calcium channel gamma-8
K05083 ERBB2, HER2, CD340; receptor tyrosine-protein kinase erbB-2 [EC:2.7.10.1 ]
K05084 ERBB3, HER3; receptor tyrosine-protein kinase erbB-3 [EC:2.7.10.1 ]
K05085 ERBB4, HER4; receptor tyrosine-protein kinase erbB-4 [EC:2.7.10.1 ]
K05087 IGF1R, CD221; insulin-like growth factor 1 receptor [EC:2.7.10.1 ]
K05089 PDGFRB, CD140B; platelet-derived growth factor receptor beta [EC:2.7.10.1 ]
K05090 CSF1R, FMS, CD115; macrophage colony-stimulating factor 1 receptor [EC:2.7.10.1 ]
K05091 KIT, SCFR, CD117; proto-oncogene tyrosine-protein kinase Kit [EC:2.7.10.1 ]
K05093 FGFR2, CD332; fibroblast growth factor receptor 2 [EC:2.7.10.1 ]
K05094 FGFR3, CD333; fibroblast growth factor receptor 3 [EC:2.7.10.1 ]
K05095 FGFR4, CD334; fibroblast growth factor receptor 4 [EC:2.7.10.1 ]
K05098 KDR, VEGFR2, CD309; kinase insert domain protein receptor [EC:2.7.10.1 ]
K05099 MET, HGFR; proto-oncogene tyrosine-protein kinase Met [EC:2.7.10.1 ]
K05121 TEK, TIE2, CD202; endothelial-specific receptor tyrosine kinase [EC:2.7.10.1 ]
K05448 VEGFA; vascular endothelial growth factor A
K05449 VEGFC_D; vascular endothelial growth factor C/D
K05450 PDGFC_D; platelet derived growth factor C/D
K05451 NGFA; nerve growth factor, alpha
K05452 GDNF; glial cell derived neurotrophic factor
K05453 CSF1, MCSF; macrophage colony-stimulating factor 1
K05454 FLT3LG; fms-related tyrosine kinase 3 ligand
K05459 IGF1; insulin-like growth factor 1
K05460 HGF; hepatocyte growth factor
K06268 PPP3R, CNB; serine/threonine-protein phosphatase 2B regulatory subunit
K07209 IKBKB, IKKB; inhibitor of nuclear factor kappa-B kinase subunit beta [EC:2.7.11.10 ]
K07210 IKBKG, IKKG, NEMO; inhibitor of nuclear factor kappa-B kinase subunit gamma
K07827 KRAS, KRAS2; GTPase KRas
K07829 RRAS; Ras-related protein R-Ras
K07830 RRAS2, TC21; Ras-related protein R-Ras2
K07831 MRAS; Ras-related protein M-Ras
K07836 RAP1B; Ras-related protein Rap-1B
K07860 RAC2; Ras-related C3 botulinum toxin substrate 2
K07861 RAC3; Ras-related C3 botulinum toxin substrate 3
K08018 RAPGEF2, PDZGEF1; Rap guanine nucleotide exchange factor 2
K08053 RASA2, GAP1M; Ras GTPase-activating protein 2
K08774 TGFA; transforming growth factor, alpha
K08845 ARAF, ARAF1; A-Raf proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1 ]
K09253 RELB; transcription factor RelB
K12326 RASGRF2; Ras-specific guanine nucleotide-releasing factor 2
K12361 RASGRP2; RAS guanyl-releasing protein 2
K12362 RASGRP3; RAS guanyl-releasing protein 3
K12363 RASGRP4; RAS guanyl-releasing protein 4
K13375 TGFB1; transforming growth factor beta-1
K13376 TGFB2; transforming growth factor beta-2
K13377 TGFB3; transforming growth factor beta-3
K13769 IGF2; insulin-like growth factor 2
K16510 RPS6KA4, MSK2; ribosomal protein S6 kinase alpha-4 [EC:2.7.11.1 ]
K16858 VEGFB; vascular endothelial growth factor B
K16859 PGF; placenta growth factor
K17333 NFATC3, NFAT4; nuclear factor of activated T-cells, cytoplasmic 3
K17386 PDGFB; platelet-derived growth factor subunit B
K17534 MLK4, KIAA1804; mitogen-activated protein kinase kinase kinase MLK4 [EC:2.7.11.25 ]
K18018 PTPN5; tyrosine-protein phosphatase non-receptor type 5 [EC:3.1.3.48 ]
K18019 PTPN7; tyrosine-protein phosphatase non-receptor type 7 [EC:3.1.3.48 ]
K18496 FGF1; fibroblast growth factor 1
K18497 FGF2; fibroblast growth factor 2
K22428 FGF23; fibroblast growth factor 23
K22429 FGF21; fibroblast growth factor 21
K22603 FGF19; fibroblast growth factor 19
Compound C01245 D-myo-Inositol 1,4,5-trisphosphate
Reference Authors Chen Z, Gibson TB, Robinson F, Silvestro L, Pearson G, Xu B, Wright A, Vanderbilt C, Cobb MH.
Title MAP kinases.
Journal Reference Authors Tanoue T, Nishida E.
Title Docking interactions in the mitogen-activated protein kinase cascades.
Journal Reference Authors Dent P, Yacoub A, Fisher PB, Hagan MP, Grant S.
Title MAPK pathways in radiation responses.
Journal Reference Authors Huang EJ, Reichardt LF.
Title Trk receptors: roles in neuronal signal transduction.
Journal Reference Authors Harper SJ, LoGrasso P.
Title Signalling for survival and death in neurones: the role of stress-activated kinases, JNK and p38.
Journal Reference Authors Takeda K, Ichijo H
Title Neuronal p38 MAPK signalling: an emerging regulator of cell fate and function in the nervous system.
Journal Reference Authors Yang SH, Sharrocks AD, Whitmarsh AJ.
Title Transcriptional regulation by the MAP kinase signaling cascades.
Journal Reference Authors Zhu X, Lee HG, Raina AK, Perry G, Smith MA.
Title The role of mitogen-activated protein kinase pathways in Alzheimer's disease.
Journal Reference Authors Cho H, Lee J, Kwak NJ, Lee KH, Rha S, Kim YH, Cho YY, Yang KH, Kim K, Lim Y.
Title Silica induces nuclear factor-kappaB activation through TAK1 and NIK in Rat2 cell line.
Journal Reference Authors Lemmon MA, Schlessinger J
Title Cell signaling by receptor tyrosine kinases.
Journal Reference Authors Skaper SD
Title The neurotrophin family of neurotrophic factors: an overview.
Journal Reference Authors Chu WM
Title Tumor necrosis factor.
Journal Reference Authors Newton K, Dixit VM
Title Signaling in innate immunity and inflammation.
Journal Reference Authors Gaestel M, Kotlyarov A, Kracht M
Title Targeting innate immunity protein kinase signalling in inflammation.
Journal Reference Authors Ajibade AA, Wang HY, Wang RF
Title Cell type-specific function of TAK1 in innate immune signaling.
Journal Reference Authors Turner MD, Nedjai B, Hurst T, Pennington DJ
Title Cytokines and chemokines: At the crossroads of cell signalling and inflammatory disease.
Journal Related ko04070 Phosphatidylinositol signaling system
