Entry
Name
MAPK signaling pathway - Homo sapiens (human)
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 transduction
BRITE hierarchy
Pathway map
Ortholog table
Network
Element
N00001 EGF-EGFR-RAS-ERK signaling pathway
N00015 PDGF-PDGFR-RAS-ERK signaling pathway
N00019 FGF-FGFR-RAS-ERK signaling pathway
N00186 IL1-IL1R-p38 signaling pathway
N00188 IL1-IL1R-JNK signaling pathway
N00215 KITLG-KIT-RAS-ERK signaling pathway
N00216 HGF-MET-RAS-ERK signaling pathway
N00217 FLT3LG-FLT3-RAS-ERK signaling pathway
N00229 TGFA-EGFR-RAS-ERK signaling pathway
N00233 IGF-IGF1R-RAS-ERK signaling pathway
N00277 EREG-EGFR-RAS-ERK signaling pathway
N00279 AREG-EGFR-RAS-ERK signaling pathway
N00542 EGF-EGFR-RAS-JNK signaling pathway
N01119 RAC/CDC42-PAK-ERK signaling pathway
N01592 GF-RTK-RAS-ERK signaling pathway
N01593 Regulation of GF-RTK-RAS-ERK signaling, PTP
N01594 MLK-JNK signaling pathway
N01597 Regulation of GF-RTK-RAS-ERK signaling, SPRED and NF1
N01600 Regulation of GF-RTK-RAS-ERK signaling, RasGAP
N01602 ERK-MYC signaling pathway
Drug
D00332 Gabapentin (JAN/USP/INN)
D00538 Zonisamide (JP18/USP/INN)
D00539 Ethosuximide (JP18/USP/INN)
D00619 Verapamil hydrochloride (JP18/USP)
D00631 Bepridil hydrochloride (USAN)
D01441 Imatinib mesylate (USAN)
D01977 Gefitinib (JP18/USAN/INN)
D02716 Pregabalin (JAN/USAN/INN)
D02970 Aprinocarsen sodium (USAN)
D03350 Canertinib dihydrochloride (USAN)
D03441 Certolizumab pegol (USAN/INN)
D03914 Dronedarone hydrochloride (USP)
D04023 Erlotinib hydrochloride (JAN/USAN)
D04024 Lapatinib ditosylate (USAN)
D04696 Lestaurtinib (USAN/INN)
D05024 Mibefradil dihydrochloride (USAN)
D05029 Midostaurin (JAN/USAN/INN)
D05380 Pazopanib hydrochloride (JAN/USAN)
D05480 Pimecrolimus (JAN/USAN/INN)
D06129 Tiapamil hydrochloride (USAN)
D06272 Sorafenib tosylate (USAN)
D06402 Sunitinib malate (JAN/USAN)
D06407 Vandetanib (JAN/USAN/INN)
D06413 Nilotinib hydrochloride hydrate (JAN)
D08344 Tozasertib lactate (USAN)
D08544 Toceranib phosphate (USAN)
D08878 Brivanib alaninate (JAN/USAN/INN)
D08883 Cediranib maleate (JAN/USAN)
D08907 Dovitinib lactate (USAN)
D08947 Motesanib diphosphate (USAN)
D08956 Omacetaxine mepesuccinate (USAN)
D09033 Voclosporin (JAN/USAN/INN)
D09539 Gabapentin enacarbil (JAN/USAN/INN)
D09603 Dilmapimod tosylate (USAN)
D09620 Fresolimumab (USAN/INN)
D09733 Afatinib dimaleate (USAN)
D09920 Lenvatinib mesylate (USAN)
D09996 Vemurafenib (JAN/USAN/INN)
D10024 Selumetinib sulfate (JAN/USAN)
D10095 Cabozantinib s-malate (USAN)
D10103 Crenolanib besylate (USAN)
D10104 Dabrafenib mesylate (USAN)
D10137 Regorafenib hydrate (JAN)
D10176 Trametinib dimethyl sulfoxide (JAN/USAN)
D10190 Tivozanib hydrochloride (USAN)
D10396 Nintedanib esylate (USAN)
D10465 Golvatinib tartrate (USAN)
D10486 Pimasertib hydrochloride (USAN)
D10604 Binimetinib (JAN/USAN/INN)
D10615 Cobimetinib fumarate (USAN)
D10766 Osimertinib mesylate (USAN)
D10790 Mirogabalin besylate (USAN)
D10959 Neflamapimod (USAN/INN)
D10988 Selonsertib (JAN/USAN/INN)
D11053 Encorafenib (JAN/USAN/INN)
D11115 Olmutinib hydrochloride (USAN)
D11139 Savolitinib (JAN/USAN/INN)
D11140 Sitravatinib (USAN/INN)
D11210 Flortaucipir F 18 (USAN)
D11270 Pexidartinib (USAN/INN)
D11271 Pexidartinib hydrochloride (JAN/USAN)
D11285 Ravoxertinib (USAN/INN)
D11289 Rivoceranib mesylate (USAN)
D11379 Edicotinib hydrochloride (USAN)
D11384 Hydromethylthionine mesylate (USAN)
D11411 Lifirafenib maleate (USAN)
D11427 Hydromethylthionine (USAN/INN)
D11434 Nazartinib mesylate (USAN)
D11452 Tomivosertib (USAN/INN)
D11481 Tomivosertib hydrochloride (USAN)
D11484 Pegcantratinib (USAN/INN)
D11541 Sitravatinib malate (USAN)
D11589 Infigratinib (USAN/INN)
D11611 Infigratinib phosphate (USAN)
D11725 Futibatinib (JAN/USAN/INN)
D11773 Tesevatinib tosylate (USAN)
D11803 Cetuximab sarotalocan (USAN/INN)
D11805 Cetuximab sarotalocan sodium (genetical recombination) (JAN)
D11874 Serclutamab talirine (USAN/INN)
D11969 Mobocertinib succinate (JAN)
D11977 Fruquintinib (JAN/USAN)
D12001 Mobocertinib (USAN/INN)
D12060 Temuterkib mesylate (USAN)
D12062 Suvecaltamide hydrocloride (USAN)
D12184 Patritumab deruxtecan (USAN/INN)
D12230 Poziotinib hydrochloride (USAN)
D12245 Lazertinib mesylate (USAN)
D12258 Aumolertinib (USAN/INN)
D12259 Aumolertinib mesylate (USAN)
D12392 Fosgonimeton (USAN/INN)
D12393 Fosgonimeton sodium (USAN)
D12409 Barzolvolimab (USAN/INN)
D12412 Emavusertib hydrochloride (USAN)
D12442 Tucatinib ethanolate (JAN)
D12456 Lirafugratinib hydrochloride (USAN)
D12457 Tuxobertinib (USAN/INN)
D12473 Zapnometinib (USAN/INN)
D12506 Sunvozertinib (USAN/INN)
D12526 Catequentinib (USAN/INN)
D12532 Emavusertib mesylate (USAN)
D12533 Emavusertib maleate (USAN)
D12537 Catequentinib hydrochloride (USAN)
D12538 Emavusertib phosphate (USAN)
D12539 emavusertib tosylate (USAN)
D12545 Tinengotinib (USAN/INN)
D12600 Bezuclastinib (USAN/INN)
D12635 Sozinibercept (USAN/INN)
D12650 Zanzalintinib (USAN/INN)
D12651 Zanzalintinib fumarate (USAN)
D12809 Bafisontamab (USAN/INN)
D12819 Ulixacaltamide (USAN/INN)
D12820 Ulixacaltamide hydrochloride (USAN)
D12854 Nilotinib laurylsulfate (USAN)
D12910 Apinocaltamide (USAN/INN)
D12922 Tizaterkib adipate (USAN)
D12939 Pimicotinib hydrochloride (USAN)
D12956 Firmonertinib (USAN/INN)
D12957 Firmonertinib mesylate (USAN)
Other DBs
Organism
Homo sapiens (human) [GN:
hsa ]
Gene
10125 RASGRP1; RAS guanyl releasing protein 1 [KO:K04350 ]
10235 RASGRP2; RAS guanyl releasing protein 2 [KO:K12361 ]
10368 CACNG3; calcium voltage-gated channel auxiliary subunit gamma 3 [KO:K04868 ]
10369 CACNG2; calcium voltage-gated channel auxiliary subunit gamma 2 [KO:K04867 ]
10454 TAB1; TGF-beta activated kinase 1 (MAP3K7) binding protein 1 [KO:K04403 ]
10912 GADD45G; growth arrest and DNA damage inducible gamma [KO:K04402 ]
11184 MAP4K1; mitogen-activated protein kinase kinase kinase kinase 1 [KO:K04408 ] [EC:2.7.11.1 ]
1147 CHUK; component of inhibitor of nuclear factor kappa B kinase complex [KO:K04467 ] [EC:2.7.11.10 ]
1386 ATF2; activating transcription factor 2 [KO:K04450 ]
1398 CRK; CRK proto-oncogene, adaptor protein [KO:K04438 ]
1399 CRKL; CRK like proto-oncogene, adaptor protein [KO:K04438 ]
1435 CSF1; colony stimulating factor 1 [KO:K05453 ]
1616 DAXX; death domain associated protein [KO:K02308 ]
1647 GADD45A; growth arrest and DNA damage inducible alpha [KO:K04402 ]
1649 DDIT3; DNA damage inducible transcript 3 [KO:K04452 ]
2002 ELK1; ETS transcription factor ELK1 [KO:K04375 ]
2005 ELK4; ETS transcription factor ELK4 [KO:K04376 ]
2255 FGF10; fibroblast growth factor 10 [KO:K04358 ]
2277 VEGFD; vascular endothelial growth factor D [KO:K05449 ]
23118 TAB2; TGF-beta activated kinase 1 (MAP3K7) binding protein 2 [KO:K04404 ]
23162 MAPK8IP3; mitogen-activated protein kinase 8 interacting protein 3 [KO:K04436 ]
2323 FLT3LG; fms related receptor tyrosine kinase 3 ligand [KO:K05454 ]
2353 FOS; Fos proto-oncogene, AP-1 transcription factor subunit [KO:K04379 ]
23542 MAPK8IP2; mitogen-activated protein kinase 8 interacting protein 2 [KO:K04435 ]
25780 RASGRP3; RAS guanyl releasing protein 3 [KO:K12362 ]
2668 GDNF; glial cell derived neurotrophic factor [KO:K05452 ]
27091 CACNG5; calcium voltage-gated channel auxiliary subunit gamma 5 [KO:K04870 ]
27092 CACNG4; calcium voltage-gated channel auxiliary subunit gamma 4 [KO:K04869 ]
2768 GNA12; G protein subunit alpha 12 [KO:K04346 ]
2885 GRB2; growth factor receptor bound protein 2 [KO:K04364 ]
3164 NR4A1; nuclear receptor subfamily 4 group A member 1 [KO:K04465 ]
3265 HRAS; HRas proto-oncogene, GTPase [KO:K02833 ]
3303 HSPA1A; heat shock protein family A (Hsp70) member 1A [KO:K03283 ]
3304 HSPA1B; heat shock protein family A (Hsp70) member 1B [KO:K03283 ]
3305 HSPA1L; heat shock protein family A (Hsp70) member 1 like [KO:K03283 ]
3310 HSPA6; heat shock protein family A (Hsp70) member 6 [KO:K03283 ]
3312 HSPA8; heat shock protein family A (Hsp70) member 8 [KO:K03283 ]
3315 HSPB1; heat shock protein family B (small) member 1 [KO:K04455 ]
3479 IGF1; insulin like growth factor 1 [KO:K05459 ]
3481 IGF2; insulin like growth factor 2 [KO:K13769 ]
355 FAS; Fas cell surface death receptor [KO:K04390 ]
3554 IL1R1; interleukin 1 receptor type 1 [KO:K04386 ]
3556 IL1RAP; interleukin 1 receptor accessory protein [KO:K04723 ]
3725 JUN; Jun proto-oncogene, AP-1 transcription factor subunit [KO:K04448 ]
3727 JUND; JunD proto-oncogene, AP-1 transcription factor subunit [KO:K04449 ]
3845 KRAS; KRAS proto-oncogene, GTPase [KO:K07827 ]
4137 MAPT; microtubule associated protein tau [KO:K04380 ]
4208 MEF2C; myocyte enhancer factor 2C [KO:K04454 ]
4609 MYC; MYC proto-oncogene, bHLH transcription factor [KO:K04377 ]
4615 MYD88; MYD88 innate immune signal transduction adaptor [KO:K04729 ]
4616 GADD45B; growth arrest and DNA damage inducible beta [KO:K04402 ]
468 ATF4; activating transcription factor 4 [KO:K04374 ]
4772 NFATC1; nuclear factor of activated T cells 1 [KO:K04446 ]
4775 NFATC3; nuclear factor of activated T cells 3 [KO:K17333 ]
4790 NFKB1; nuclear factor kappa B subunit 1 [KO:K02580 ]
4791 NFKB2; nuclear factor kappa B subunit 2 [KO:K04469 ]
4804 NGFR; nerve growth factor receptor [KO:K02583 ]
4893 NRAS; NRAS proto-oncogene, GTPase [KO:K07828 ]
5154 PDGFA; platelet derived growth factor subunit A [KO:K04359 ]
5155 PDGFB; platelet derived growth factor subunit B [KO:K17386 ]
5534 PPP3R1; protein phosphatase 3 regulatory subunit B, alpha [KO:K06268 ]
5535 PPP3R2; protein phosphatase 3 regulatory subunit B, beta [KO:K06268 ]
55799 CACNA2D3; calcium voltage-gated channel auxiliary subunit alpha2delta 3 [KO:K04860 ]
56034 PDGFC; platelet derived growth factor C [KO:K05450 ]
5871 MAP4K2; mitogen-activated protein kinase kinase kinase kinase 2 [KO:K04414 ] [EC:2.7.11.1 ]
5906 RAP1A; RAP1A, member of RAS oncogene family [KO:K04353 ]
5908 RAP1B; RAP1B, member of RAS oncogene family [KO:K07836 ]
5921 RASA1; RAS p21 protein activator 1 [KO:K04352 ]
5922 RASA2; RAS p21 protein activator 2 [KO:K08053 ]
5923 RASGRF1; Ras protein specific guanine nucleotide releasing factor 1 [KO:K04349 ]
5924 RASGRF2; Ras protein specific guanine nucleotide releasing factor 2 [KO:K12326 ]
59283 CACNG8; calcium voltage-gated channel auxiliary subunit gamma 8 [KO:K04873 ]
59284 CACNG7; calcium voltage-gated channel auxiliary subunit gamma 7 [KO:K04872 ]
59285 CACNG6; calcium voltage-gated channel auxiliary subunit gamma 6 [KO:K04871 ]
5970 RELA; RELA proto-oncogene, NF-kB subunit [KO:K04735 ]
5971 RELB; RELB proto-oncogene, NF-kB subunit [KO:K09253 ]
627 BDNF; brain derived neurotrophic factor [KO:K04355 ]
6654 SOS1; SOS Ras/Rac guanine nucleotide exchange factor 1 [KO:K03099 ]
6655 SOS2; SOS Ras/Rho guanine nucleotide exchange factor 2 [KO:K03099 ]
7039 TGFA; transforming growth factor alpha [KO:K08774 ]
7040 TGFB1; transforming growth factor beta 1 [KO:K13375 ]
7042 TGFB2; transforming growth factor beta 2 [KO:K13376 ]
7043 TGFB3; transforming growth factor beta 3 [KO:K13377 ]
7132 TNFRSF1A; TNF receptor superfamily member 1A [KO:K03158 ]
7422 VEGFA; vascular endothelial growth factor A [KO:K05448 ]
7423 VEGFB; vascular endothelial growth factor B [KO:K16858 ]
7424 VEGFC; vascular endothelial growth factor C [KO:K05449 ]
773 CACNA1A; calcium voltage-gated channel subunit alpha1 A [KO:K04344 ]
774 CACNA1B; calcium voltage-gated channel subunit alpha1 B [KO:K04849 ]
775 CACNA1C; calcium voltage-gated channel subunit alpha1 C [KO:K04850 ]
776 CACNA1D; calcium voltage-gated channel subunit alpha1 D [KO:K04851 ]
777 CACNA1E; calcium voltage-gated channel subunit alpha1 E [KO:K04852 ]
778 CACNA1F; calcium voltage-gated channel subunit alpha1 F [KO:K04853 ]
779 CACNA1S; calcium voltage-gated channel subunit alpha1 S [KO:K04857 ]
781 CACNA2D1; calcium voltage-gated channel auxiliary subunit alpha2delta 1 [KO:K04858 ]
782 CACNB1; calcium voltage-gated channel auxiliary subunit beta 1 [KO:K04862 ]
783 CACNB2; calcium voltage-gated channel auxiliary subunit beta 2 [KO:K04863 ]
784 CACNB3; calcium voltage-gated channel auxiliary subunit beta 3 [KO:K04864 ]
785 CACNB4; calcium voltage-gated channel auxiliary subunit beta 4 [KO:K04865 ]
786 CACNG1; calcium voltage-gated channel auxiliary subunit gamma 1 [KO:K04866 ]
80310 PDGFD; platelet derived growth factor D [KO:K05450 ]
8074 FGF23; fibroblast growth factor 23 [KO:K22428 ]
8491 MAP4K3; mitogen-activated protein kinase kinase kinase kinase 3 [KO:K04406 ] [EC:2.7.11.1 ]
8517 IKBKG; inhibitor of nuclear factor kappa B kinase regulatory subunit gamma [KO:K07210 ]
8649 LAMTOR3; late endosomal/lysosomal adaptor, MAPK and MTOR activator 3 [KO:K04370 ]
8717 TRADD; TNFRSF1A associated via death domain [KO:K03171 ]
8817 FGF18; fibroblast growth factor 18 [KO:K04358 ]
8822 FGF17; fibroblast growth factor 17 [KO:K04358 ]
8823 FGF16; fibroblast growth factor 16 [KO:K04358 ]
8911 CACNA1I; calcium voltage-gated channel subunit alpha1 I [KO:K04856 ]
8912 CACNA1H; calcium voltage-gated channel subunit alpha1 H [KO:K04855 ]
8913 CACNA1G; calcium voltage-gated channel subunit alpha1 G [KO:K04854 ]
9254 CACNA2D2; calcium voltage-gated channel auxiliary subunit alpha2delta 2 [KO:K04859 ]
93589 CACNA2D4; calcium voltage-gated channel auxiliary subunit alpha2delta 4 [KO:K04861 ]
9448 MAP4K4; mitogen-activated protein kinase kinase kinase kinase 4 [KO:K04407 ] [EC:2.7.11.1 ]
9479 MAPK8IP1; mitogen-activated protein kinase 8 interacting protein 1 [KO:K04434 ]
9693 RAPGEF2; Rap guanine nucleotide exchange factor 2 [KO:K08018 ]
9965 FGF19; fibroblast growth factor 19 [KO:K22603 ]
998 CDC42; cell division cycle 42 [KO:K04393 ]
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 pathway
hsa04070 Phosphatidylinositol signaling system
KO pathway