KEGG   PATHWAY: ocu04010
Entry
ocu04010                    Pathway                                
Name
MAPK signaling pathway - Oryctolagus cuniculus (rabbit)
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
Pathway map
ocu04010  MAPK signaling pathway
ocu04010

Disease
H02157  Short-rib thoracic dysplasia
Other DBs
GO: 0000165
Organism
Oryctolagus cuniculus (rabbit) [GN:ocu]
Gene
100008607  KDR; vascular endothelial growth factor receptor 2 precursor [KO:K05098] [EC:2.7.10.1]
100008609  FAS; tumor necrosis factor receptor superfamily member 6 precursor [KO:K04390]
100008645  TGFB1; transforming growth factor beta-1 proprotein [KO:K13375]
100008668  IGF1; insulin-like growth factor I precursor [KO:K05459]
100008681  FGF7; fibroblast growth factor 7 precursor [KO:K04358]
100008748  PLA2G4A; cytosolic phospholipase A2 [KO:K16342] [EC:3.1.1.4]
100008806  [KO:K04361] [EC:2.7.10.1]
100008807  [KO:K05084] [EC:2.7.10.1]
100008808  [KO:K04357]
100008815  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
100008829  [KO:K05097] [EC:2.7.10.1]
100008834  [KO:K04358]
100008840  CASP3; caspase-3 [KO:K02187] [EC:3.4.22.56]
100008856  JUN; transcription factor Jun [KO:K04448]
100008859  [KO:K17333]
100008899  [KO:K05448]
100008911  [KO:K04527] [EC:2.7.10.1]
100008912  PDGFD; platelet-derived growth factor D [KO:K05450]
100008965  [KO:K04393]
100008979  CACNA1B; voltage-dependent N-type calcium channel subunit alpha-1B [KO:K04849]
100008983  CD14; monocyte differentiation antigen CD14 precursor [KO:K04391]
100008990  IL1B; interleukin-1 beta precursor [KO:K04519]
100009028  KITLG; kit ligand precursor [KO:K05461]
100009068  [KO:K18497]
100009088  TNF; tumor necrosis factor precursor [KO:K03156]
100009102  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
100009105  CACNA2D1; voltage-dependent calcium channel subunit alpha-2/delta-1 preproprotein [KO:K04858]
100009109  CACNB1; voltage-dependent L-type calcium channel subunit beta-1 [KO:K04862]
100009235  [KO:K04439]
100009250  IL1A; interleukin-1 alpha [KO:K04383]
100009263  CACNG1; voltage-dependent calcium channel gamma-1 subunit [KO:K04866]
100009265  CACNA1A; voltage-dependent P/Q-type calcium channel subunit alpha-1A [KO:K04344]
100009277  CACNB2; voltage-dependent L-type calcium channel subunit beta-2 [KO:K04863]
100009292  TP53; cellular tumor antigen p53 [KO:K04451]
100009316  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
100009328  [KO:K05085] [EC:2.7.10.1]
100009371  TGFB2; transforming growth factor beta-2 proprotein precursor [KO:K13376]
100009402  CACNB3; voltage-dependent L-type calcium channel subunit beta-3 [KO:K04864]
100009403  CACNA1E; voltage-dependent R-type calcium channel subunit alpha-1E [KO:K04852]
100009417  FGFR2; fibroblast growth factor receptor 2 precursor [KO:K05093] [EC:2.7.10.1]
100009423  PPP3CA; protein phosphatase 3 catalytic subunit alpha [KO:K04348] [EC:3.1.3.16]
100009431  PPM1A; protein phosphatase 1A [KO:K04457] [EC:3.1.3.16]
100009438  [KO:K04443] [EC:2.7.11.1]
100009482  [KO:K08774]
100009487  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform [KO:K04348] [EC:3.1.3.16]
100009535  PAK2; serine/threonine-protein kinase PAK 2 [KO:K04410] [EC:2.7.11.1]
100009554  [KO:K05083] [EC:2.7.10.1]
100009585  CACNA1S; voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857]
100037719  PRKCB; protein kinase C beta type isoform I [KO:K19662] [EC:2.7.11.13]
100037720  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
100101555  CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C [KO:K04850]
100126565  MET; hepatocyte growth factor receptor precursor [KO:K05099] [EC:2.7.10.1]
100144342  [KO:K05087] [EC:2.7.10.1]
100316906  FGF5; fibroblast growth factor 5 isoform X1 [KO:K04358]
100316908  HGF; hepatocyte growth factor precursor [KO:K05460]
100327259  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D isoform X1 [KO:K04851]
100327263  KIT; mast/stem cell growth factor receptor Kit [KO:K05091] [EC:2.7.10.1]
100327265  MYC; myc proto-oncogene protein [KO:K04377]
100328754  FLNA; filamin-A [KO:K04437]
100328756  RA_M006_JSM7BED4F; FLNA protein [KO:K04437]
100328774  CACNG7; voltage-dependent calcium channel gamma-7 subunit [KO:K04872]
100328792  IGF2; insulin-like growth factor II precursor [KO:K13769]
100328898  FGF1; fibroblast growth factor 1 [KO:K18496]
100328905  IKBKG; NF-kappa-B essential modulator [KO:K07210]
100337888  [KO:K03171]
100337999  [KO:K04440] [EC:2.7.11.24]
100338014  [KO:K04373] [EC:2.7.11.1]
100338059  [KO:K12326]
100338090  [KO:K05449]
100338160  [KO:K03283]
100338211  [KO:K05449]
100338345  [KO:K04379]
100338439  [KO:K04452]
100338535  [KO:K04464] [EC:2.7.11.24]
100338577  [KO:K05453]
100338772  [KO:K04869]
100338774  [KO:K04442] [EC:2.7.11.1]
100339005  [KO:K04381]
100339021  [KO:K04870]
100339320  [KO:K02308]
100339383  [KO:K04374]
100339515  [KO:K16859]
100339873  [KO:K04392]
100339891  [KO:K07836]
100339910  [KO:K04372] [EC:2.7.11.1]
100339928  [KO:K04469]
100339953  [KO:K04432] [EC:2.7.12.2]
100340353  [KO:K04349]
100340437  [KO:K08845] [EC:2.7.11.1]
100340478  [KO:K04358]
100340494  [KO:K04859]
100340498  [KO:K04426] [EC:2.7.11.25]
100340517  [KO:K16342] [EC:3.1.1.4]
100340710  [KO:K05126] [EC:2.7.10.1]
100340775  [KO:K16342] [EC:3.1.1.4]
100340811  [KO:K04729]
100340952  [KO:K04375]
100340992  [KO:K05090] [EC:2.7.10.1]
100340993  [KO:K21278] [EC:3.1.3.16 3.1.3.48]
100341033  PLA2G4E; cytosolic phospholipase A2 epsilon [KO:K16342] [EC:3.1.1.4]
100341204  [KO:K04439]
100341237  [KO:K16342] [EC:3.1.1.4]
100341281  [KO:K04723]
100341605  [KO:K04733] [EC:2.7.11.1]
100341695  [KO:K04441] [EC:2.7.11.24]
100341731  [KO:K04417] [EC:2.7.11.25]
100341883  [KO:K04373] [EC:2.7.11.1]
100342183  [KO:K12362]
100342212  [KO:K04345] [EC:2.7.11.11]
100342232  [KO:K04453]
100342249  [KO:K04404]
100342292  [KO:K04444] [EC:2.7.11.1]
100342327  [KO:K04438]
100342471  [KO:K18019] [EC:3.1.3.48]
100342500  [KO:K04364]
100342573  [KO:K04429] [EC:2.7.11.1]
100342664  [KO:K04440] [EC:2.7.11.24]
100342742  [KO:K04358]
100342781  [KO:K05465]
100342802  [KO:K04358]
100342852  [KO:K04456] [EC:2.7.11.1]
100342872  [KO:K05089] [EC:2.7.10.1]
100342958  [KO:K04429] [EC:2.7.11.1]
100343006  [KO:K04363] [EC:2.7.10.1]
100343050  [KO:K22428]
100343069  [KO:K04425] [EC:2.7.11.25]
100343162  [KO:K04459] [EC:3.1.3.16 3.1.3.48]
100343190  [KO:K03175] [EC:2.3.2.27]
100343228  [KO:K04462] [EC:2.1.1.367]
100343352  [KO:K05096] [EC:2.7.10.1]
100343398  [KO:K04352]
100343410  [KO:K09784]
100343518  [KO:K05103] [EC:2.7.10.1]
100343571  [KO:K04427] [EC:2.7.11.25]
100343621  [KO:K04418] [EC:2.7.11.25]
100344003  [KO:K04380]
100344073  [KO:K04389]
100344161  [KO:K04441] [EC:2.7.11.24]
100344224  [KO:K04865]
100344241  [KO:K07828]
100344335  TGFBR2; TGF-beta receptor type-2 precursor [KO:K04388] [EC:2.7.11.30]
100344451  [KO:K04373] [EC:2.7.11.1]
100344482  [KO:K04393]
100344533  [KO:K06268]
100344706  [KO:K04434]
100344731  [KO:K04459] [EC:3.1.3.16 3.1.3.48]
100344852  [KO:K04430] [EC:2.7.12.2]
100344921  [KO:K05462]
100345073  [KO:K04356]
100345167  [KO:K04454]
100345602  [KO:K04422] [EC:2.7.11.25]
100345607  MAP3K21; mitogen-activated protein kinase kinase kinase 21 [KO:K17534] [EC:2.7.11.25]
100345812  [KO:K04674] [EC:2.7.11.30]
100346106  [KO:K03158]
100346309  [KO:K04854]
100346367  [KO:K04358]
100346391  [KO:K03099]
100346752  [KO:K08018]
100346929  [KO:K04440] [EC:2.7.11.24]
100347293  [KO:K04346]
100347345  [KO:K04371] [EC:2.7.11.24]
100347407  [KO:K04366] [EC:2.7.11.1]
100347487  [KO:K07827]
100347524  [KO:K17614] [EC:3.1.3.16 3.1.3.48]
100348164  [KO:K04376]
100348305  [KO:K05467]
100348484  [KO:K04416] [EC:2.7.11.25]
100348520  [KO:K04445] [EC:2.7.11.1]
100348561  [KO:K04371] [EC:2.7.11.24]
100348873  [KO:K03283]
100348930  [KO:K04468] [EC:2.7.11.24]
100349095  [KO:K02583]
100349186  [KO:K04373] [EC:2.7.11.1]
100349426  [KO:K02580]
100349438  [KO:K08052]
100349787  [KO:K04429] [EC:2.7.11.1]
100349994  [KO:K04465]
100350075  [KO:K04868]
100350272  [KO:K05450]
100350483  [KO:K04867]
100350559  [KO:K12363]
100350614  [KO:K04441] [EC:2.7.11.24]
100350814  [KO:K04408] [EC:2.7.11.1]
100351032  [KO:K04466] [EC:2.7.11.25]
100351238  [KO:K04458] [EC:3.1.3.48]
100351327  [KO:K04860]
100351542  [KO:K04459] [EC:3.1.3.16 3.1.3.48]
100351588  [KO:K04353]
100351826  MAP3K20; mitogen-activated protein kinase kinase kinase 20 isoform X1 [KO:K04424] [EC:2.7.11.25]
100351861  [KO:K04362] [EC:2.7.10.1]
100351877  [KO:K04871]
100351964  [KO:K04365] [EC:2.7.11.1]
100352056  [KO:K04409] [EC:2.7.11.1]
100352279  [KO:K20216] [EC:3.1.3.16 3.1.3.48]
100352301  [KO:K13375]
100352378  [KO:K04446]
100352388  [KO:K04359]
100352548  [KO:K04360] [EC:2.7.10.1]
100352677  [KO:K25415]
100352814  [KO:K18498] [EC:3.1.3.16 3.1.3.48]
100352905  [KO:K04386]
100353284  [KO:K04402]
100353377  [KO:K05466]
100353534  [KO:K03283]
100353641  [KO:K04435]
100353706  [KO:K04456] [EC:2.7.11.1]
100353742  [KO:K04402]
100353754  [KO:K04459] [EC:3.1.3.16 3.1.3.48]
100354037  [KO:K03283]
100354108  [KO:K04861]
100354143  [KO:K04460] [EC:3.1.3.16]
100354292  [KO:K03176] [EC:2.7.10.1]
100354435  [KO:K03283]
100354523  [KO:K04455]
100354550  [KO:K09782]
100354695  [KO:K04378]
100354743  [KO:K04730] [EC:2.7.11.1]
100355017  [KO:K04405]
100355129  [KO:K05452]
100355175  [KO:K12457]
100355230  [KO:K04433] [EC:2.7.12.2]
100355275  [KO:K05095] [EC:2.7.10.1]
100355324  [KO:K04421] [EC:2.7.11.25]
100355367  [KO:K04450]
100355438  [KO:K04407] [EC:2.7.11.1]
100355566  [KO:K04415] [EC:2.7.11.25]
100355690  [KO:K21946] [EC:3.1.3.16 3.1.3.48]
100355693  [KO:K04420] [EC:2.7.11.25]
100355861  [KO:K04358]
100355888  [KO:K04467] [EC:2.7.11.10]
100355920  [KO:K07830]
100356245  [KO:K04348] [EC:3.1.3.16]
100356340  [KO:K22429]
100356354  [KO:K04406] [EC:2.7.11.1]
100356401  [KO:K07209] [EC:2.7.11.10]
100356520  [KO:K07860]
100356572  [KO:K03283]
100356615  [KO:K03099]
100356616  [KO:K04461] [EC:3.1.3.16]
100356675  [KO:K05121] [EC:2.7.10.1]
100356691  [KO:K04419] [EC:2.7.11.25]
100356949  [KO:K04355]
100357261  [KO:K04853]
100357503  [KO:K08053]
100357564  [KO:K04412]
100358004  [KO:K05462]
100358104  [KO:K04428] [EC:2.7.11.25]
100358158  [KO:K04423] [EC:2.7.11.25]
100358182  [KO:K07831]
100358230  [KO:K04459] [EC:3.1.3.16 3.1.3.48]
100358241  [KO:K04381]
100358246  [KO:K04403]
100358702  [KO:K04373] [EC:2.7.11.1]
100358715  [KO:K04463] [EC:2.7.12.2]
100358772  [KO:K17386]
100358822  [KO:K04411]
100358959  [KO:K05462]
100358982  [KO:K13377]
100358984  [KO:K05096] [EC:2.7.10.1]
100359020  [KO:K18018] [EC:3.1.3.48]
100359319  [KO:K04350]
100533118  PLA2G4B; cytosolic phospholipase A2 beta [KO:K16342] [EC:3.1.1.4]
103345313  [KO:K04431] [EC:2.7.12.2]
103345448  [KO:K13375]
103345488  [KO:K04358]
103346035  [KO:K04441] [EC:2.7.11.24]
103346112  [KO:K04873]
103346323  [KO:K09253]
103346567  [KO:K05454]
103346785  [KO:K16510] [EC:2.7.11.1]
103347298  [KO:K04436]
103348219  [KO:K05866] [EC:3.1.3.48]
103348976  [KO:K04459] [EC:3.1.3.16 3.1.3.48]
103350046  [KO:K05462]
103350089  [KO:K02582]
103350153  [KO:K04347]
103350744  [KO:K04370]
108175474  [KO:K05092] [EC:2.7.10.1]
108176185  GNG14; putative guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-14 [KO:K04347]
127484946  [KO:K18018] [EC:3.1.3.48]
127485184  [KO:K04735]
127485863  [KO:K05094] [EC:2.7.10.1]
127486116  [KO:K04456] [EC:2.7.11.1]
127486605  [KO:K02833]
127486621  [KO:K04372] [EC:2.7.11.1]
127487461  [KO:K16858]
127488490  [KO:K04455]
127488889  [KO:K03283]
127488890  [KO:K03283]
127489207  [KO:K05462]
127489236  [KO:K07827]
127489362  [KO:K07829]
127489461  [KO:K04368] [EC:2.7.12.2]
127491144  [KO:K05084] [EC:2.7.10.1]
127493068  [KO:K03283]
Compound
C00076  Calcium cation
C00165  Diacylglycerol
C00338  Lipopolysaccharide
C00575  3',5'-Cyclic AMP
C01245  D-myo-Inositol 1,4,5-trisphosphate
Reference
PMID:11749383
  Authors
Chen Z, Gibson TB, Robinson F, Silvestro L, Pearson G, Xu B, Wright A, Vanderbilt C, Cobb MH.
  Title
MAP kinases.
  Journal
Chem Rev 101:2449-76 (2001)
DOI:10.1021/cr000241p
Reference
PMID:12191611
  Authors
Tanoue T, Nishida E.
  Title
Docking interactions in the mitogen-activated protein kinase cascades.
  Journal
Pharmacol Ther 93:193-202 (2002)
DOI:10.1016/S0163-7258(02)00188-2
Reference
PMID:12947395
  Authors
Dent P, Yacoub A, Fisher PB, Hagan MP, Grant S.
  Title
MAPK pathways in radiation responses.
  Journal
Oncogene 22:5885-96 (2003)
DOI:10.1038/sj.onc.1206701
Reference
PMID:12676795
  Authors
Huang EJ, Reichardt LF.
  Title
Trk receptors: roles in neuronal signal transduction.
  Journal
Annu Rev Biochem 72:609-42 (2003)
DOI:10.1146/annurev.biochem.72.121801.161629
Reference
PMID:11369511
  Authors
Harper SJ, LoGrasso P.
  Title
Signalling for survival and death in neurones: the role of stress-activated kinases, JNK and p38.
  Journal
Cell Signal 13:299-310 (2001)
DOI:10.1016/S0898-6568(01)00148-6
Reference
PMID:12390245
  Authors
Takeda K, Ichijo H
  Title
Neuronal p38 MAPK signalling: an emerging regulator of cell fate and function in the nervous system.
  Journal
Genes Cells 7:1099-111 (2002)
DOI:10.1046/j.1365-2443.2002.00591.x
Reference
PMID:14597384
  Authors
Yang SH, Sharrocks AD, Whitmarsh AJ.
  Title
Transcriptional regulation by the MAP kinase signaling cascades.
  Journal
Gene 320:3-21 (2003)
DOI:10.1016/S0378-1119(03)00816-3
Reference
PMID:12566928
  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
Neurosignals 11:270-81 (2002)
DOI:10.1159/000067426
Reference
PMID:12849693
  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
Toxicol Lett 143:323-30 (2003)
DOI:10.1016/S0378-4274(03)00193-0
Reference
PMID:20602996
  Authors
Lemmon MA, Schlessinger J
  Title
Cell signaling by receptor tyrosine kinases.
  Journal
Cell 141:1117-34 (2010)
DOI:10.1016/j.cell.2010.06.011
Reference
PMID:22367796
  Authors
Skaper SD
  Title
The neurotrophin family of neurotrophic factors: an overview.
  Journal
Methods Mol Biol 846:1-12 (2012)
DOI:10.1007/978-1-61779-536-7_1
Reference
PMID:23085193
  Authors
Chu WM
  Title
Tumor necrosis factor.
  Journal
Cancer Lett 328:222-5 (2013)
DOI:10.1016/j.canlet.2012.10.014
Reference
PMID:22296764
  Authors
Newton K, Dixit VM
  Title
Signaling in innate immunity and inflammation.
  Journal
Cold Spring Harb Perspect Biol 4:a006049 (2012)
DOI:10.1101/cshperspect.a006049
Reference
PMID:19483709
  Authors
Gaestel M, Kotlyarov A, Kracht M
  Title
Targeting innate immunity protein kinase signalling in inflammation.
  Journal
Nat Rev Drug Discov 8:480-99 (2009)
DOI:10.1038/nrd2829
Reference
PMID:23664135
  Authors
Ajibade AA, Wang HY, Wang RF
  Title
Cell type-specific function of TAK1 in innate immune signaling.
  Journal
Trends Immunol 34:307-16 (2013)
DOI:10.1016/j.it.2013.03.007
Reference
PMID:24892271
  Authors
Turner MD, Nedjai B, Hurst T, Pennington DJ
  Title
Cytokines and chemokines: At the crossroads of cell signalling and inflammatory disease.
  Journal
Biochim Biophys Acta 1843:2563-2582 (2014)
DOI:10.1016/j.bbamcr.2014.05.014
Related
pathway
ocu04070  Phosphatidylinositol signaling system
ocu04110  Cell cycle
ocu04115  p53 signaling pathway
ocu04210  Apoptosis
ocu04310  Wnt signaling pathway
ocu04668  TNF signaling pathway
KO pathway
ko04010   

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