Entry
Name
MAPK signaling pathway - Xenopus laevis (African clawed frog)
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
Other DBs
Organism
Xenopus laevis (African clawed frog) [GN:
xla ]
Gene
100036935 cacng1.L; calcium channel, voltage-dependent, gamma subunit 1 L homeolog [KO:K04866 ]
100037058 vegfa.S; vascular endothelial growth factor A S homeolog precursor [KO:K05448 ]
100037194 ecsit.S; evolutionarily conserved signaling intermediate in Toll pathway, mitochondrial precursor [KO:K04405 ]
100127255 cacnb1.S; voltage-dependent L-type calcium channel subunit beta-1 isoform X1 [KO:K04862 ]
100137626 tnfrsf1a.S; TNF receptor superfamily member 1A S homeolog precursor [KO:K03158 ]
100158413 mapt.S; microtubule-associated protein tau isoform X2 [KO:K04380 ]
100190767 elk1.S; ELK1, member of ETS oncogene family S homeolog [KO:K04375 ]
100337571 gdnf.S; glial cell derived neurotrophic factor S homeolog precursor [KO:K05452 ]
100381020 hspa1a.S; heat shock protein family A (Hsp70) member 1A S homeolog [KO:K03283 ]
100381102 ppp3cc.L; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348 ] [EC:3.1.3.16 ]
100381134 cacna1s.S; voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857 ]
100462911 cacna1c.S; voltage-dependent L-type calcium channel subunit alpha-1C isoform X11 [KO:K04850 ]
100462912 cacna1d.L; voltage-dependent L-type calcium channel subunit alpha-1D isoform X1 [KO:K04851 ]
100462913 cacna1f.L; voltage-dependent L-type calcium channel subunit alpha-1D isoform X3 [KO:K04853 ]
100462914 cacna1g.L; voltage-dependent T-type calcium channel subunit alpha-1G isoform X6 [KO:K04854 ]
100462915 cacna1h.L; voltage-dependent T-type calcium channel subunit alpha-1H isoform X2 [KO:K04855 ]
100462926 cacna1b.S; voltage-dependent N-type calcium channel subunit alpha-1B isoform X3 [KO:K04849 ]
100462927 cacna1e.L; voltage-dependent R-type calcium channel subunit alpha-1E isoform X1 [KO:K04852 ]
100462928 cacna1i.L; voltage-dependent T-type calcium channel subunit alpha-1I isoform X1 [KO:K04856 ]
101027271 gadd45b.S; growth arrest and DNA damage inducible beta S homeolog [KO:K04402 ]
101243553 csf1.S; colony stimulating factor-1 S homeolog precursor [KO:K05453 ]
108695211 nfatc1.S; nuclear factor of activated T-cells, cytoplasmic 1 isoform X2 [KO:K04446 ]
108696066 tnfrsf1a.L; tumor necrosis factor receptor superfamily member 1A [KO:K03158 ]
108696243 nfkb2.L; nuclear factor NF-kappa-B p100 subunit-like isoform X1 [KO:K04469 ]
108696277 XB5893022.L; protransforming growth factor alpha isoform X1 [KO:K08774 ]
108696777 cacng7.L; voltage-dependent calcium channel gamma-7 subunit isoform X1 [KO:K04872 ]
108696778 cacng8.L; voltage-dependent calcium channel gamma-8 subunit [KO:K04873 ]
108696811 hspa1a.L; heat shock cognate 71 kDa protein-like isoform X1 [KO:K03283 ]
108697660 cdc42.S; cell division control protein 42 homolog isoform X1 [KO:K04393 ]
108697821 cacng7.S; voltage-dependent calcium channel gamma-7 subunit [KO:K04872 ]
108697822 cacng8.S; voltage-dependent calcium channel gamma-8 subunit [KO:K04873 ]
108698108 elk1.L; ETS domain-containing protein Elk-1 isoform X2 [KO:K04375 ]
108699715 rasgrp1.S; RAS guanyl-releasing protein 1-like isoform X1 [KO:K04350 ]
108700276 tgfb1.S; transforming growth factor beta-1 proprotein-like [KO:K13375 ]
108700783 cacnb1.L; voltage-dependent L-type calcium channel subunit beta-1 isoform X2 [KO:K04862 ]
108701210 cacng4.L; voltage-dependent calcium channel gamma-4 subunit [KO:K04869 ]
108701386 atf2.L; cyclic AMP-dependent transcription factor ATF-2 isoform X2 [KO:K04450 ]
108701573 pdgfa.L; platelet-derived growth factor subunit A-like isoform X2 [KO:K04359 ]
108701906 cacng3.L; voltage-dependent calcium channel gamma-3 subunit [KO:K04868 ]
108702163 cacng4.S; voltage-dependent calcium channel gamma-4 subunit [KO:K04869 ]
108702165 cacng1.S; voltage-dependent calcium channel gamma-1 subunit [KO:K04866 ]
108703170 mapk8ip3.S; C-Jun-amino-terminal kinase-interacting protein 3 [KO:K04436 ]
108703206 cacng3.S; voltage-dependent calcium channel gamma-3 subunit [KO:K04868 ]
108704004 cacna2d3.L; voltage-dependent calcium channel subunit alpha-2/delta-3 isoform X1 [KO:K04860 ]
108704565 cacna1c.L; voltage-dependent L-type calcium channel subunit alpha-1C isoform X1 [KO:K04850 ]
108705261 ppp3cc.S; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X2 [KO:K04348 ] [EC:3.1.3.16 ]
108707236 mef2c.S; myocyte-specific enhancer factor 2C isoform X1 [KO:K04454 ]
108711204 cacna2d1.L; voltage-dependent calcium channel subunit alpha-2/delta-1 isoform X5 [KO:K04858 ]
108711263 mapk8ip2.L; C-Jun-amino-terminal kinase-interacting protein 2 [KO:K04435 ]
108712402 gadd45b.L; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402 ]
108712658 map2k7.S; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431 ] [EC:2.7.12.2 ]
108713013 mapk8ip2.S; C-Jun-amino-terminal kinase-interacting protein 2 isoform X1 [KO:K04435 ]
108713061 cacna2d1.S; voltage-dependent calcium channel subunit alpha-2/delta-1 isoform X8 [KO:K04858 ]
108713974 nfatc3.L; nuclear factor of activated T-cells, cytoplasmic 3 isoform X1 [KO:K17333 ]
108714209 gadd45a.L; growth arrest and DNA damage-inducible protein GADD45 alpha isoform X1 [KO:K04402 ]
108714259 artn.L; glial cell line-derived neurotrophic factor-like [KO:K25415 ]
108714525 pdgfb.L; platelet-derived growth factor subunit B isoform X1 [KO:K17386 ]
108714609 cacna2d2.L; voltage-dependent calcium channel subunit alpha-2/delta-2 isoform X1 [KO:K04859 ]
108715004 faslg.S; tumor necrosis factor ligand superfamily member 6 [KO:K04389 ]
108715019 cacna1i.S; voltage-dependent T-type calcium channel subunit alpha-1I isoform X1 [KO:K04856 ]
108715251 fgf3.S; fibroblast growth factor 3 S homeolog precursor [KO:K04358 ]
108715518 gng12.S; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-12 [KO:K04347 ]
108715550 artn.S; glial cell line-derived neurotrophic factor-like isoform X1 [KO:K25415 ]
108715765 tab1.S; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 [KO:K04403 ]
108715833 cacna2d2.S; voltage-dependent calcium channel subunit alpha-2/delta-2 isoform X2 [KO:K04859 ]
108716751 tab2.L; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 [KO:K04404 ]
108716971 il1rap.L; interleukin-1 receptor accessory protein isoform X1 [KO:K04723 ]
108717706 tgfb2.S; transforming growth factor beta-2 proprotein-like isoform X1 [KO:K13376 ]
108717890 tab2.S; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 isoform X1 [KO:K04404 ]
108718047 il1rap.S; interleukin-1 receptor accessory protein isoform X2 [KO:K04723 ]
108718812 cacnb2.L; voltage-dependent L-type calcium channel subunit beta-2 isoform X5 [KO:K04863 ]
108719866 cacnb2.S; voltage-dependent L-type calcium channel subunit beta-2 isoform X5 [KO:K04863 ]
373551 met.L; MET proto-oncogene, receptor tyrosine kinase L homeolog precursor [KO:K05099 ] [EC:2.7.10.1 ]
373569 fgf10.S; fibroblast growth factor 10 S homeolog [KO:K04358 ]
373579 kit.L; mast/stem cell growth factor receptor-related protein Kit precursor [KO:K05091 ] [EC:2.7.10.1 ]
373589 vegfa.L; vascular endothelial growth factor A L homeolog precursor [KO:K05448 ]
373616 cacnb3.S; calcium channel, voltage-dependent, beta 3 subunit S homeolog [KO:K04864 ]
373669 fgf3.L; fibroblast growth factor 3 precursor [KO:K04358 ]
373674 nr4a1.L; nuclear receptor subfamily 4 group A member 1 [KO:K04465 ]
373727 g67.L; mast/stem cell growth factor receptor-related protein Kit-like [KO:K05091 ] [EC:2.7.10.1 ]
373772 kit.S; KIT proto-oncogene receptor tyrosine kinase S homeolog precursor [KO:K05091 ] [EC:2.7.10.1 ]
373777 cacna2d3.S; calcium channel, voltage-dependent, alpha 2/delta subunit 3 S homeolog precursor [KO:K04860 ]
373801 tgfb2.L; transforming growth factor beta-2 proprotein precursor [KO:K13376 ]
373821 ngfr.S; tumor necrosis factor receptor superfamily member 16 [KO:K02583 ]
373828 cacna1a.S; voltage-dependent P/Q-type calcium channel subunit alpha-1A isoform X1 [KO:K04344 ]
378546 cacnb3.L; calcium channel, voltage-dependent, beta 3 subunit L homeolog [KO:K04864 ]
378586 fgf4.L; fibroblast growth factor 4A precursor [KO:K04358 ]
378587 fgf4.S; fibroblast growth factor 4B precursor [KO:K04358 ]
378644 elk4.S; ELK4, ETS transcription factor S homeolog [KO:K04376 ]
378663 relb.S; transcription factor RelB homolog [KO:K09253 ]
379055 cdc42.L; cell division cycle 42 L homeolog [KO:K04393 ]
379224 gadd45a.S; growth arrest and DNA damage inducible alpha S homeolog [KO:K04402 ]
379250 rasgrp2.S; RAS guanyl-releasing protein 2-A [KO:K12361 ]
379285 gadd45g.S; uncharacterized protein LOC379285 [KO:K04402 ]
379319 hspa8.L; heat shock protein family A (Hsp70) member 8 L homeolog [KO:K03283 ]
379557 lamtor3.L; ragulator complex protein LAMTOR3-B [KO:K04370 ]
379760 hspa1l.S; heat shock protein family A (Hsp70) member 1 like S homeolog [KO:K03283 ]
379851 nr4a1.S; nuclear receptor subfamily 4 group A member 1 S homeolog [KO:K04465 ]
379991 map2k1.L; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368 ] [EC:2.7.12.2 ]
380388 prkacb.S; protein kinase cAMP-activated catalytic subunit beta S homeolog [KO:K04345 ] [EC:2.7.11.11 ]
380570 lamtor3-like.L; ragulator complex protein LAMTOR3-A [KO:K04370 ]
394321 myd88.L; myeloid differentiation primary response protein MyD88-A [KO:K04729 ]
394353 rela.L; putative transcription factor p65 homolog [KO:K04735 ]
394391 map2k7.L; dual specificity mitogen-activated protein kinase kinase 7 [KO:K04431 ] [EC:2.7.12.2 ]
397698 nfkb2.S; nuclear factor NF-kappa-B p100 subunit [KO:K04469 ]
397765 pdgfa.S; platelet-derived growth factor subunit A precursor [KO:K04359 ]
397771 kras.L; kirsten rat sarcoma viral oncogene homolog L homeolog [KO:K07827 ]
397778 tgfb1.L; transforming growth factor beta-1 proprotein precursor [KO:K13375 ]
398025 tab1.L; TGF-beta activated kinase 1/MAP3K7 binding protein 1 L homeolog [KO:K04403 ]
398129 ngfr.L; nerve growth factor receptor L homeolog precursor [KO:K02583 ]
398134 nradd.L; neurotrophin receptor associated death domain L homeolog precursor [KO:K02583 ]
398240 igf2.S; insulin-like growth factor II-A precursor [KO:K13769 ]
398245 igf3.L; insulin-like growth factor III precursor [KO:K13769 ]
398297 nfatc3.S; nuclear factor of activated T cells 3 S homeolog [KO:K17333 ]
398307 mapt.L; microtubule-associated protein tau [KO:K04380 ]
398615 ddit3.L; DNA damage inducible transcript 3 L homeolog [KO:K04452 ]
398804 atf4.L; activating transcription factor 4 L homeolog [KO:K04374 ]
398925 stk4.S; serine/threonine-protein kinase 4 [KO:K04411 ]
399105 fgf20.L; fibroblast growth factor 20 L homeolog [KO:K04358 ]
399183 fgf8.L; fibroblast growth factor 8 L homeolog precursor [KO:K04358 ]
399196 gadd45g.L; growth arrest and DNA damage inducible gamma L homeolog [KO:K04402 ]
399295 tgfbr1.S; transforming growth factor beta receptor I S homeolog precursor [KO:K04674 ] [EC:2.7.11.30 ]
399379 rac3.S; Rac family small GTPase 3 S homeolog [KO:K04392 ]
399406 hras.L; Harvey rat sarcoma viral oncogene homolog L homeolog [KO:K02833 ]
399458 grb2.L; growth factor receptor-bound protein 2-A [KO:K04364 ]
399471 map2k4.L; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04430 ] [EC:2.7.12.2 ]
414290 rap1a.S; RAP1A, member of RAS oncogene family S homeolog [KO:K04353 ]
414479 rasgrp1.L; RAS guanyl-releasing protein 1 isoform X1 [KO:K04350 ]
414569 crkl.S; uncharacterized protein LOC414569 [KO:K04438 ]
431908 map2k4.S; dual specificity mitogen-activated protein kinase kinase 2-like [KO:K04430 ] [EC:2.7.12.2 ]
432106 ppp3cb.L; protein phosphatase 3, catalytic subunit, beta isozyme L homeolog [KO:K04348 ] [EC:3.1.3.16 ]
432200 ikbkb.L; inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase beta L homeolog [KO:K07209 ] [EC:2.7.11.10 ]
432206 igf2.L; insulin-like growth factor II-B precursor [KO:K13769 ]
432210 stk3.S; serine/threonine-protein kinase 3 [KO:K04412 ]
432338 nradd.S; neurotrophin receptor associated death domain S homeolog precursor [KO:K02583 ]
443932 mras.L; muscle RAS oncogene homolog L homeolog [KO:K07831 ]
444095 grb2.S; growth factor receptor-bound protein 2-B [KO:K04364 ]
444184 rac2.L; Rac family small GTPase 2 L homeolog [KO:K07860 ]
444230 angpt1.S; angiopoietin 1 S homeolog precursor [KO:K05465 ]
444310 mef2c.L; MADS box transcription enhancer factor 2, polypeptide C (myocyte enhancer factor 2C) L homeolog [KO:K04454 ]
444346 nfatc1.L; nuclear factor of activated T cells 1 L homeolog [KO:K04446 ]
444537 elk4.L; ELK4, ETS transcription factor L homeolog [KO:K04376 ]
444605 cacng5.L; calcium channel, voltage-dependent, gamma subunit 5 L homeolog [KO:K04870 ]
444638 ntf3.S; neurotrophin 3 S homeolog precursor [KO:K04356 ]
446279 daxx.L; death-associated protein 6 L homeolog [KO:K02308 ]
447008 rasgrp2.L; RAS guanyl-releasing protein 2-B [KO:K12361 ]
447105 hspb1.S; heat shock protein family B (small) member 1 S homeolog [KO:K04455 ]
447107 hspb1.L; heat shock protein family B (small) member 1 L homeolog [KO:K04455 ]
447196 ppp3ca.L; protein phosphatase 3, catalytic subunit, alpha isozyme L homeolog [KO:K04348 ] [EC:3.1.3.16 ]
447201 fos.S; FBJ murine osteosarcoma viral oncogene homolog S homeolog [KO:K04379 ]
447229 rapgef2.L; Rap guanine nucleotide exchange factor 2 L homeolog [KO:K08018 ]
447419 crkl.L; v-crk avian sarcoma virus CT10 oncogene homolog-like L homeolog [KO:K04438 ]
447632 nfkb1.L; nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 L homeolog [KO:K02580 ]
493575 pdgfb.S; platelet-derived growth factor subunit B [KO:K17386 ]
494866 rasgrf1.S; ras-specific guanine nucleotide-releasing factor 1 isoform X2 [KO:K04349 ]
496037 tgfa.L; transforming growth factor alpha L homeolog precursor [KO:K08774 ]
595043 gng12.L; guanine nucleotide binding protein (G protein), gamma 12 L homeolog [KO:K04347 ]
733418 tradd.L; tumor necrosis factor receptor type 1-associated DEATH domain protein [KO:K03171 ]
734165 atf4.S; activating transcription factor 4 S homeolog [KO:K04374 ]
734302 myd88.S; myeloid differentiation primary response protein MyD88-B [KO:K04729 ]
734331 vegfc.S; vascular endothelial growth factor C S homeolog precursor [KO:K05449 ]
734336 map3k22.L; mitogen-activated protein kinase kinase kinase 22 L homeolog [KO:K04421 ] [EC:2.7.11.25 ]
734382 rac1.L; Rac family small GTPase 1 L homeolog [KO:K04392 ]
734697 fgf7.L; fibroblast growth factor 7 L homeolog [KO:K04358 ]
735069 ikbkg.L; inhibitor of nuclear factor kappa B kinase subunit gamma L homeolog [KO:K07210 ]
779087 gdnf.L; glial cell line-derived neurotrophic factor precursor [KO:K05452 ]
779127 rap1a.L; RAP1A, member of RAS oncogene family L homeolog [KO:K04353 ]
779173 ntrk2.S; neurotrophic receptor tyrosine kinase 2 S homeolog precursor [KO:K04360 ] [EC:2.7.10.1 ]
779226 stk4.L; serine/threonine kinase 4 L homeolog [KO:K04411 ]
779370 fgfr3.L; fibroblast growth factor receptor 3 (achondroplasia, thanatophoric dwarfism) L homeolog [KO:K05094 ] [EC:2.7.10.1 ]
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
xla04070 Phosphatidylinositol signaling system
KO pathway