Entry
Name
MAPK signaling pathway - Rattus norvegicus (rat)
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
Other DBs
Organism
Rattus norvegicus (rat) [GN:
rno ]
Gene
25398 Cacna1a; voltage-dependent P/Q-type calcium channel subunit alpha-1A [KO:K04344 ]
257648 Cacna1b; voltage-dependent N-type calcium channel subunit alpha-1B isoform 1 [KO:K04849 ]
24239 Cacna1c; voltage-dependent L-type calcium channel subunit alpha-1C [KO:K04850 ]
29716 Cacna1d; voltage-dependent L-type calcium channel subunit alpha-1D [KO:K04851 ]
54234 Cacna1e; voltage-dependent R-type calcium channel subunit alpha-1E [KO:K04852 ]
114493 Cacna1f; voltage-dependent L-type calcium channel subunit alpha-1F [KO:K04853 ]
29717 Cacna1g; voltage-dependent T-type calcium channel subunit alpha-1G isoform 1 [KO:K04854 ]
114862 Cacna1h; voltage-dependent T-type calcium channel subunit alpha-1H [KO:K04855 ]
56827 Cacna1i; voltage-dependent T-type calcium channel subunit alpha-1I [KO:K04856 ]
682930 Cacna1s; voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857 ]
25399 Cacna2d1; voltage-dependent calcium channel subunit alpha-2/delta-1 isoform 3 precursor [KO:K04858 ]
300992 Cacna2d2; voltage-dependent calcium channel subunit alpha-2/delta-2 precursor [KO:K04859 ]
306243 Cacna2d3; voltage-dependent calcium channel subunit alpha-2/delta-3 precursor [KO:K04860 ]
312668 Cacna2d4; voltage-dependent calcium channel subunit alpha-2/delta-4 [KO:K04861 ]
50688 Cacnb1; voltage-dependent L-type calcium channel subunit beta-1 [KO:K04862 ]
116600 Cacnb2; voltage-dependent L-type calcium channel subunit beta-2 isoform 2 [KO:K04863 ]
25297 Cacnb3; voltage-dependent L-type calcium channel subunit beta-3 [KO:K04864 ]
58942 Cacnb4; voltage-dependent L-type calcium channel subunit beta-4 isoform 2 [KO:K04865 ]
29658 Cacng1; voltage-dependent calcium channel gamma-1 subunit [KO:K04866 ]
84347 Cacng2; voltage-dependent calcium channel gamma-2 subunit [KO:K04867 ]
140724 Cacng3; voltage-dependent calcium channel gamma-3 subunit [KO:K04868 ]
140725 Cacng4; voltage-dependent calcium channel gamma-4 subunit [KO:K04869 ]
140726 Cacng5; voltage-dependent calcium channel gamma-5 subunit [KO:K04870 ]
140727 Cacng6; voltage-dependent calcium channel gamma-6 subunit [KO:K04871 ]
140728 Cacng7; voltage-dependent calcium channel gamma-7 subunit [KO:K04872 ]
140729 Cacng8; voltage-dependent calcium channel gamma-8 subunit [KO:K04873 ]
81663 Gna12; guanine nucleotide-binding protein subunit alpha-12 [KO:K04346 ]
114120 Gng12; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-12 [KO:K04347 ]
685513 Gng14; putative guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-14 [KO:K04347 ]
24675 Ppp3cb; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform [KO:K04348 ] [EC:3.1.3.16 ]
171378 Ppp3cc; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform [KO:K04348 ] [EC:3.1.3.16 ]
192213 Rasgrf1; ras-specific guanine nucleotide-releasing factor 1 isoform 1 [KO:K04349 ]
114513 Rasgrf2; ras-specific guanine nucleotide-releasing factor 2 [KO:K12326 ]
29434 Rasgrp1; RAS guanyl-releasing protein 1 [KO:K04350 ]
310533 Rapgef2; rap guanine nucleotide exchange factor 2 [KO:K08018 ]
25676 Rasa1; ras GTPase-activating protein 1 [KO:K04352 ]
25597 Rasa2; ras GTPase-activating protein 2 [KO:K08053 ]
171337 Rap1b; ras-related protein Rap-1b precursor [KO:K07836 ]
25313 Egf; pro-epidermal growth factor precursor [KO:K04357 ]
24827 Tgfa; protransforming growth factor alpha preproprotein [KO:K08774 ]
170633 Fgf3; fibroblast growth factor 3 precursor [KO:K04358 ]
116499 Fgf4; fibroblast growth factor 4 precursor [KO:K04358 ]
60662 Fgf5; fibroblast growth factor 5 isoform 1 precursor [KO:K04358 ]
29348 Fgf7; fibroblast growth factor 7 precursor [KO:K04358 ]
25443 Fgf10; fibroblast growth factor 10 precursor [KO:K04358 ]
29368 Fgf17; fibroblast growth factor 17 isoform 1 precursor [KO:K04358 ]
29369 Fgf18; fibroblast growth factor 18 precursor [KO:K04358 ]
170579 Fgf22; fibroblast growth factor 22 precursor [KO:K04358 ]
170582 Fgf19; fibroblast growth factor 19 precursor [KO:K22603 ]
170580 Fgf21; fibroblast growth factor 21 precursor [KO:K22429 ]
170583 Fgf23; fibroblast growth factor 23 precursor [KO:K22428 ]
24225 Bdnf; brain-derived neurotrophic factor isoform 3 preproprotein [KO:K04355 ]
81737 Ntf3; neurotrophin-3 isoform 3 precursor [KO:K04356 ]
24482 Igf1; insulin-like growth factor I isoform d preproprotein [KO:K05459 ]
24483 Igf2; insulin-like growth factor II isoform 2 preproprotein [KO:K13769 ]
25266 Pdgfa; platelet-derived growth factor subunit A precursor [KO:K04359 ]
24628 Pdgfb; platelet-derived growth factor subunit B precursor [KO:K17386 ]
79429 Pdgfc; platelet-derived growth factor C precursor [KO:K05450 ]
66018 Pdgfd; platelet-derived growth factor D precursor [KO:K05450 ]
78965 Csf1; macrophage colony-stimulating factor 1 precursor [KO:K05453 ]
60427 Kitlg; kit ligand isoform 1 precursor [KO:K05461 ]
103691134 Flt3lg; fms-related tyrosine kinase 3 ligand precursor [KO:K05454 ]
83785 Vegfa; vascular endothelial growth factor A isoform 6 precursor [KO:K05448 ]
89811 Vegfb; vascular endothelial growth factor B precursor [KO:K16858 ]
94203 Pgf; placenta growth factor precursor [KO:K16859 ]
114111 Vegfc; vascular endothelial growth factor C precursor [KO:K05449 ]
360457 Vegfd; vascular endothelial growth factor D precursor [KO:K05449 ]
24446 Hgf; hepatocyte growth factor preproprotein [KO:K05460 ]
25453 Gdnf; glial cell line-derived neurotrophic factor isoform 1 [KO:K05452 ]
24596 Ngfr; tumor necrosis factor receptor superfamily member 16 precursor [KO:K02583 ]
25718 Igf1r; insulin-like growth factor 1 receptor isoform 2 precursor [KO:K05087 ] [EC:2.7.10.1 ]
25267 Pdgfra; platelet-derived growth factor receptor alpha precursor [KO:K04363 ] [EC:2.7.10.1 ]
54251 Flt1; vascular endothelial growth factor receptor 1 isoform 2 precursor [KO:K05096 ] [EC:2.7.10.1 ]
24716 Ret; proto-oncogene tyrosine-protein kinase receptor Ret isoform a precursor [KO:K05126 ] [EC:2.7.10.1 ]
81504 Grb2; growth factor receptor-bound protein 2 [KO:K04364 ]
367858 Hrasl1; HRas proto-oncogene, GTPase like 1 [KO:K02833 ]
58960 Map2k2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369 ] [EC:2.7.12.2 ]
362045 Lamtor3; ragulator complex protein LAMTOR3 [KO:K04370 ]
79255 Atf4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374 ]
314436 Elk1; ETS domain-containing protein Elk-1 [KO:K04375 ]
304786 Elk4; ETS domain-containing protein Elk-4 [KO:K04376 ]
29477 Mapt; microtubule-associated protein tau [KO:K04380 ]
59086 Tgfb1; transforming growth factor beta-1 proprotein precursor [KO:K13375 ]
81809 Tgfb2; transforming growth factor beta-2 proprotein precursor [KO:K13376 ]
25717 Tgfb3; transforming growth factor beta-3 proprotein preproprotein [KO:K13377 ]
25625 Tnfrsf1a; tumor necrosis factor receptor superfamily member 1A precursor [KO:K03158 ]
25663 Il1r1; interleukin-1 receptor type 1 precursor [KO:K04386 ]
25466 Il1rap; interleukin-1 receptor accessory protein precursor [KO:K04723 ]
25385 Faslg; tumor necrosis factor ligand superfamily member 6 [KO:K04389 ]
246097 Fas; tumor necrosis factor receptor superfamily member 6 precursor [KO:K04390 ]
60350 Cd14; monocyte differentiation antigen CD14 precursor [KO:K04391 ]
363875 Rac1; ras-related C3 botulinum toxin substrate 1 [KO:K04392 ]
366957 Rac2; ras-related C3 botulinum toxin substrate 2 [KO:K07860 ]
64465 Cdc42; cell division control protein 42 homolog [KO:K04393 ]
246756 Tradd; tumor necrosis factor receptor type 1-associated DEATH domain protein [KO:K03171 ]
301059 Myd88; myeloid differentiation primary response protein MyD88 [KO:K04729 ]
25112 Gadd45a; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402 ]
291005 Gadd45g; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402 ]
299626 Gadd45b; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402 ]
315139 Tab1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 [KO:K04403 ]
308267 Tab2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 [KO:K04404 ]
300447 Ecsit; evolutionarily conserved signaling intermediate in Toll pathway, mitochondrial precursor [KO:K04405 ]
301363 Map4k4; mitogen-activated protein kinase kinase kinase kinase 4 isoform 1 [KO:K04407 ] [EC:2.7.11.1 ]
65189 Stk3; serine/threonine-protein kinase 3 [KO:K04412 ]
293694 Map4k2; mitogen-activated protein kinase kinase kinase kinase 2 isoform 1 [KO:K04414 ] [EC:2.7.11.1 ]
363855 Map2k7; dual specificity mitogen-activated protein kinase kinase 7 isoform 1 [KO:K04431 ] [EC:2.7.12.2 ]
116457 Mapk8ip1; C-Jun-amino-terminal kinase-interacting protein 1 [KO:K04434 ]
315220 Mapk8ip2; C-Jun-amino-terminal kinase-interacting protein 2 [KO:K04435 ]
302983 Mapk8ip3; C-Jun-amino-terminal kinase-interacting protein 3 [KO:K04436 ]
100361818 Nfatc1; nuclear factor of activated T-cells, cytoplasmic 1 isoform 1 [KO:K04446 ]
361400 Nfatc3; nuclear factor of activated T-cells, cytoplasmic 3 [KO:K17333 ]
24518 Jund; transcription factor JunD isoform JunD-FL [KO:K04449 ]
81647 Atf2; cyclic AMP-dependent transcription factor ATF-2 [KO:K04450 ]
29467 Ddit3; DNA damage-inducible transcript 3 protein [KO:K04452 ]
499497 Mef2c; myocyte-specific enhancer factor 2C isoform 1 [KO:K04454 ]
94202 Ptprr; receptor-type tyrosine-protein phosphatase R isoform 1 precursor [KO:K04458 ] [EC:3.1.3.48 ]
24468 Hspa8; heat shock cognate 71 kDa protein [KO:K03283 ]
24963 Hspa1l; heat shock 70 kDa protein 1-like [KO:K03283 ]
29568 Map2k5; dual specificity mitogen-activated protein kinase kinase 5 isoform a [KO:K04463 ] [EC:2.7.12.2 ]
79240 Nr4a1; nuclear receptor subfamily 4 group A member 1 [KO:K04465 ]
81736 Nfkb1; nuclear factor NF-kappa-B p105 subunit isoform 2 [KO:K02580 ]
309452 Nfkb2; nuclear factor NF-kappa-B p100 subunit [KO:K04469 ]
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
rno04070 Phosphatidylinositol signaling system
KO pathway