Mapk signaling pathway (WP493)

Mus musculus

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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. Source: KEGG http://www.genome.jp/dbget-bin/www_bget?pathway:map04010

Authors

Sebastien Burel , Kristina Hanspers , Daniela Digles , Martina Summer-Kutmon , Denise Slenter , and Eric Weitz

Activity

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Organisms

Mus musculus

Communities

Annotations

Pathway Ontology

mitogen activated protein kinase signaling pathway

Participants

Label Type Compact URI Comment
cAMP Metabolite hmdb:HMDB0000058
Tgfbr2 GeneProduct ncbigene:21813
Dusp1 GeneProduct ncbigene:19252
Mapkapk5 GeneProduct ncbigene:17165
Elk1 GeneProduct ncbigene:13712
Tmem37 GeneProduct ncbigene:170706
Ecsit GeneProduct ncbigene:26940
Rasgrf2 GeneProduct ncbigene:19418
Crkl GeneProduct ncbigene:12929
Arrb2 GeneProduct ncbigene:216869
Rps6ka3 GeneProduct ncbigene:110651
Map3k11 GeneProduct ncbigene:26403
Stmn1 GeneProduct ncbigene:16765
Rasa1 GeneProduct ncbigene:218397
Casp7 GeneProduct ncbigene:12369
Ptpn7 GeneProduct ncbigene:320139
Taok2 GeneProduct mgi:MGI:1915919
Trp53 GeneProduct ncbigene:22059
Ptpn7 GeneProduct ncbigene:320139
Il1r1 GeneProduct ncbigene:16177
Casp6 GeneProduct ncbigene:12368
Egfr GeneProduct ncbigene:13649
Akt2 GeneProduct ncbigene:11652
Tnf GeneProduct ncbigene:21926
Ddit3 GeneProduct ncbigene:13198
Crk GeneProduct ncbigene:12928
Hspb2 GeneProduct ncbigene:69253
Nr4a1 GeneProduct ncbigene:15370
Fgf4 GeneProduct ncbigene:14175
Cd14 GeneProduct ncbigene:12475
Atf4 GeneProduct ncbigene:11911
Fasl GeneProduct ncbigene:14103
B230120H23Rik GeneProduct ncbigene:65964
Gadd45a GeneProduct ncbigene:13197
Tgfbr1 GeneProduct ncbigene:21812
Ppp3ca GeneProduct ncbigene:19055
Casp3 GeneProduct ncbigene:12367
Map3k7ip2 GeneProduct ncbigene:68652
Prkcc GeneProduct ncbigene:18752
Map3k7 GeneProduct ncbigene:26409
Stk3 GeneProduct ncbigene:56274
Casp8 GeneProduct ncbigene:12370
Arrb1 GeneProduct ncbigene:109689
Rasgrp1 GeneProduct ncbigene:19419
Elk1 GeneProduct ncbigene:13712
Grb2 GeneProduct ncbigene:14784
Acvr1c GeneProduct ncbigene:269275
Ikbkg GeneProduct ncbigene:16151
Braf GeneProduct ncbigene:109880
Mapk9 GeneProduct ncbigene:26420
Srf GeneProduct ncbigene:20807
Mapk13 GeneProduct ncbigene:26415
Map3k14 GeneProduct ncbigene:53859
Pla2g10 GeneProduct ncbigene:26565
Map3k1 GeneProduct ncbigene:26401
Ptprr GeneProduct ncbigene:19279
Pdgfrb GeneProduct ncbigene:18596
Map2k2 GeneProduct ncbigene:26396
Tgfb3 GeneProduct ncbigene:21809
Ptpn5 GeneProduct ncbigene:19259
Kras GeneProduct ncbigene:16653
Ptpn5 GeneProduct ncbigene:19259
Ppm1a GeneProduct ncbigene:19042
Il1a GeneProduct ncbigene:16175
Cdc25b GeneProduct ncbigene:12531
Fos GeneProduct ncbigene:14281
Prkch GeneProduct ncbigene:18755
Ntf5 GeneProduct ncbigene:78405
Casp9 GeneProduct ncbigene:12371
Mos GeneProduct ncbigene:17451
Ikbkb GeneProduct ncbigene:16150
Hspb1 GeneProduct ncbigene:15507
Acvr1b GeneProduct ncbigene:11479
Akt1 GeneProduct ncbigene:11651
Map3k6 GeneProduct ncbigene:53608
Ppp3r2 GeneProduct ncbigene:19059
Mink1 GeneProduct ncbigene:50932
Cdc42 GeneProduct ncbigene:12540
Raf1 GeneProduct ncbigene:110157
Mapk6 GeneProduct ncbigene:50772
Mapk7 GeneProduct ncbigene:23939
Map3k5 GeneProduct ncbigene:26408
Prkcd GeneProduct ncbigene:18753
Nras GeneProduct ncbigene:18176
Prkcb GeneProduct ncbigene:18751
Mapk10 GeneProduct ncbigene:26414
Atf2 GeneProduct ncbigene:11909
Map3k12 GeneProduct ncbigene:26404
Egf GeneProduct ncbigene:13645
Nlk GeneProduct ncbigene:18099
Jun GeneProduct ncbigene:16476
Atf4 GeneProduct ncbigene:11911
Map3k4 GeneProduct ncbigene:26407
Map4k3 GeneProduct ncbigene:225028
Mapk1 GeneProduct ncbigene:26413
Map3k13 GeneProduct ncbigene:71751
Tgfb2 GeneProduct ncbigene:21808
Hspa1a GeneProduct ncbigene:193740
Pla2g5 GeneProduct ncbigene:18784
Taok1 GeneProduct ncbigene:216965
Map2k1 GeneProduct ncbigene:26395
Dusp10 GeneProduct ncbigene:63953
Ngf GeneProduct ncbigene:18049
Ppm1b GeneProduct ncbigene:19043
Mapkapk2 GeneProduct ncbigene:17164
Hspa5 GeneProduct ncbigene:14828
Dusp6 GeneProduct ncbigene:67603
Mapk8ip3 GeneProduct ncbigene:30957
Dusp4 GeneProduct ncbigene:319520
Pak2 GeneProduct ncbigene:224105
Map2k4 GeneProduct ncbigene:26398
Mapk4 GeneProduct ncbigene:225724
Dusp5 GeneProduct ncbigene:240672
Ppp5c GeneProduct ncbigene:19060
Rap1a GeneProduct ncbigene:109905
Ppp3r1 GeneProduct ncbigene:19058
Map4k4 GeneProduct ncbigene:26921
Myc GeneProduct ncbigene:17869
Map3k7ip1 GeneProduct ncbigene:66513
Hspa8 GeneProduct ncbigene:15481
Tgfb1 GeneProduct ncbigene:21803
Daxx GeneProduct ncbigene:13163
Nfkb1 GeneProduct ncbigene:18033
Mapk3 GeneProduct ncbigene:26417
Rasgrp4 GeneProduct ncbigene:233046
Mapt GeneProduct ncbigene:17762
Map2k6 GeneProduct ncbigene:26399
Prkcz GeneProduct ncbigene:18762
Gck GeneProduct ncbigene:103988
Nf1 GeneProduct ncbigene:18015
Akt3 GeneProduct ncbigene:23797
Ppp3cb GeneProduct ncbigene:19056
Rac2 GeneProduct ncbigene:19354
Casp1 GeneProduct ncbigene:12362
Bdnf GeneProduct ncbigene:12064
Pak1 GeneProduct ncbigene:18479
Mapk8 GeneProduct ncbigene:26419
Il1r2 GeneProduct ncbigene:16178
Prkaca GeneProduct ncbigene:18747
Mapk14 GeneProduct ncbigene:26416
Traf2 GeneProduct ncbigene:22030
Map2k7 GeneProduct ncbigene:26400
Ppp3cc GeneProduct ncbigene:19057
Rap1b GeneProduct ncbigene:215449
Mapk12 GeneProduct ncbigene:29857
Traf6 GeneProduct ncbigene:22034
Ntrk1 GeneProduct ncbigene:18211
Map3k8 GeneProduct ncbigene:26410
Mras GeneProduct ncbigene:17532
Il1b GeneProduct ncbigene:16176
Sos2 GeneProduct ncbigene:20663
Dusp7 GeneProduct ncbigene:235584
Rasa2 GeneProduct ncbigene:114713
Gna12 GeneProduct ncbigene:14673
Casp2 GeneProduct ncbigene:12366
Rac1 GeneProduct ncbigene:19353
Mef2c GeneProduct ncbigene:17260
Map4k1 GeneProduct ncbigene:26411
Prkcd GeneProduct ncbigene:18753
Pdgfb GeneProduct ncbigene:18591
Ptprr GeneProduct ncbigene:19279
Map2k5 GeneProduct ncbigene:23938
Fas GeneProduct ncbigene:14102
Flna GeneProduct ncbigene:192176
Max GeneProduct ncbigene:17187
Jund GeneProduct ncbigene:16478

References

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  3. MAP kinases. Chen Z, Gibson TB, Robinson F, Silvestro L, Pearson G, Xu B, et al. Chem Rev. 2001 Aug;101(8):2449–76. PubMed Europe PMC Scholia
  4. Docking interactions in the mitogen-activated protein kinase cascades. Tanoue T, Nishida E. Pharmacol Ther. 2002;93(2–3):193–202. PubMed Europe PMC Scholia
  5. Neuronal p38 MAPK signalling: an emerging regulator of cell fate and function in the nervous system. Takeda K, Ichijo H. Genes Cells. 2002 Nov;7(11):1099–111. PubMed Europe PMC Scholia
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  8. Silica induces nuclear factor-kappaB activation through TAK1 and NIK in Rat2 cell line. Cho H, Lee J, Kwak NJ, Lee KH, Rha S, Kim YH, et al. Toxicol Lett. 2003 Aug 28;143(3):323–30. PubMed Europe PMC Scholia
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  10. Transcriptional regulation by the MAP kinase signaling cascades. Yang SH, Sharrocks AD, Whitmarsh AJ. Gene. 2003 Nov 27;320:3–21. PubMed Europe PMC Scholia
  11. MEKK4 stimulation of p38 and JNK activity is negatively regulated by GSK3beta. Abell AN, Granger DA, Johnson GL. J Biol Chem. 2007 Oct 19;282(42):30476–84. PubMed Europe PMC Scholia
  12. GST pi modulates JNK activity through a direct interaction with JNK substrate, ATF2. Thévenin AF, Zony CL, Bahnson BJ, Colman RF. Protein Sci. 2011 May;20(5):834–48. PubMed Europe PMC Scholia