MAPK signaling pathway (WP382)

Homo sapiens

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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. Description reference: KEGG http://www.genome.jp/dbget-bin/www_bget?pathway:map04010 Proteins on this pathway have targeted assays available via the [https://assays.cancer.gov/available_assays?wp_id=WP382 CPTAC Assay Portal]

Authors

Sebastien Burel , Kristina Hanspers , Bingo , Martijn Van Iersel , Alex Pico , Daniela Digles , Martina Summer-Kutmon , Zahra Roudbari , Denise Slenter , Egon Willighagen , and Eric Weitz

Activity

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Organisms

Homo sapiens

Communities

CPTAC PancCanNet

Annotations

Pathway Ontology

mitogen activated protein kinase signaling pathway mitogen activated protein kinase signaling pathway

Participants
Query Drugst.One

Label Type Compact URI Comment
LPS Metabolite chebi:16412
IP3 Metabolite chebi:16595
Ca2+ Metabolite hmdb:HMDB0000464
cAMP Metabolite hmdb:HMDB0000058
Ca2+ Metabolite hmdb:HMDB0000464
DAG Metabolite chebi:18035
TRAF6 GeneProduct ncbigene:7189
MEF2C GeneProduct ncbigene:4208
SRF GeneProduct ncbigene:6722
RPS6KA3 GeneProduct ncbigene:6197
MAP2K3 GeneProduct ncbigene:5606
ELK4 GeneProduct ensembl:ENSG00000158711
RAP1A GeneProduct ncbigene:5906
CRK GeneProduct ncbigene:1398
IL1A GeneProduct ncbigene:3552
PDGFB GeneProduct ncbigene:5155
AKT3 GeneProduct ncbigene:10000
ECSIT GeneProduct ncbigene:51295
MAP3K13 GeneProduct ncbigene:9175
RASGRP4 GeneProduct ncbigene:115727
MAP3K7 GeneProduct ncbigene:6885
MAPK9 GeneProduct ncbigene:5601
GRB2 GeneProduct ncbigene:2885
MKNK1 GeneProduct ncbigene:8569
DUSP1 GeneProduct ncbigene:1843
STMN1 GeneProduct ncbigene:3925
ELK1 GeneProduct ncbigene:2002
EGFR GeneProduct ncbigene:1956
PPP3CB GeneProduct ncbigene:5532
PPP3CC GeneProduct ncbigene:5533
MAP4K1 GeneProduct ncbigene:11184
NFATC1 GeneProduct ncbigene:4772
ARRB2 GeneProduct ncbigene:409
MAPT GeneProduct ncbigene:4137
RASGRP1 GeneProduct ncbigene:10125
RAP1B GeneProduct ncbigene:5908
CD14 GeneProduct ncbigene:929
IKBKG GeneProduct ncbigene:8517
BDNF GeneProduct ncbigene:627
DAXX GeneProduct ncbigene:1616
MAPK10 GeneProduct ncbigene:5602
TNF GeneProduct ncbigene:7124
ARAF GeneProduct ensembl:ENSG00000078061
STK4 GeneProduct ensembl:ENSG00000101109
MAPK14 GeneProduct ncbigene:1432
IKBKB GeneProduct ncbigene:3551
ARRB1 GeneProduct ncbigene:408
LRRK2 GeneProduct ensembl:ENSG00000188906
CASP3 GeneProduct ncbigene:836
FLNA GeneProduct ncbigene:2316
PRKACA GeneProduct ncbigene:5566
MAPKAPK2 GeneProduct ncbigene:9261
TNFRSF1A GeneProduct ensembl:ENSG00000067182
MAP3K14 GeneProduct ensembl:ENSG00000006062
HSPB1 GeneProduct ncbigene:3315
ZAK GeneProduct ncbigene:51776
GNA12 GeneProduct ncbigene:2768
TGFB1 GeneProduct ncbigene:7040
MAP3K1 GeneProduct ncbigene:4214
MAP3K2 GeneProduct ncbigene:10746
MAX GeneProduct ncbigene:4149
DUSP10 GeneProduct ncbigene:11221
RASGRF2 GeneProduct ncbigene:5924
MAP4K4 GeneProduct ncbigene:9448
PDGFRB GeneProduct ncbigene:5159
TAB1 GeneProduct ncbigene:10454
MAP3K4 GeneProduct ncbigene:4216
GADD45A GeneProduct ncbigene:1647
MAP2K5 GeneProduct ncbigene:5607
CDC25B GeneProduct ncbigene:994
IL1R1 GeneProduct ncbigene:3554
RAC2 GeneProduct ncbigene:5880
PRKCD GeneProduct ncbigene:5580
PPP5C GeneProduct ncbigene:5536
MAP2K1 GeneProduct ncbigene:5604
RAC1 GeneProduct ncbigene:5879
PTPN7 GeneProduct ncbigene:5778
IL1R2 GeneProduct ncbigene:7850
TAB2 GeneProduct ncbigene:23118
TGFBR1 GeneProduct ncbigene:7046
MAPK1 GeneProduct ncbigene:5594
PTPRR GeneProduct ncbigene:5801
PTPN5 GeneProduct ncbigene:84867
PLA2G4D GeneProduct ensembl:ENSG00000159337
BRAF GeneProduct ncbigene:673
NTRK1 GeneProduct ncbigene:4914
ATF2 GeneProduct ncbigene:1386
MAP2K4 GeneProduct ncbigene:6416
FOS GeneProduct ncbigene:2353
PRKCG GeneProduct ncbigene:5582
MYC GeneProduct ncbigene:4609
SOS2 GeneProduct ncbigene:6655
TGFB2 GeneProduct ncbigene:7042
ELK1 GeneProduct ncbigene:2002
MAPK7 GeneProduct ncbigene:5598
DUSP4 GeneProduct ncbigene:1846
CACNG3 GeneProduct hgnc.symbol:CACNG3
HSPA8 GeneProduct ncbigene:3312
MAPK12 GeneProduct ncbigene:6300
MAPK8IP1 GeneProduct ensembl:ENSG00000121653
PPM1A GeneProduct ncbigene:5494
IL1B GeneProduct ncbigene:3553
ELK4 GeneProduct ensembl:ENSG00000158711
TRAF2 GeneProduct ncbigene:7186
MAPK13 GeneProduct ncbigene:5603
TAOK1 GeneProduct ncbigene:57551
MAP2K6 GeneProduct ncbigene:5608
DUSP8 GeneProduct ensembl:ENSG00000184545
AKT2 GeneProduct ncbigene:208
MAPKAPK5 GeneProduct ncbigene:8550
RASA2 GeneProduct ncbigene:5922
DUSP7 GeneProduct ncbigene:1849
PPP3R2 GeneProduct ncbigene:5535
FGFR1 GeneProduct ncbigene:2260
TGFB3 GeneProduct ncbigene:7043
PPP3CA GeneProduct ncbigene:5530
EGF GeneProduct ncbigene:1950
DDIT3 GeneProduct ncbigene:1649
MAP3K6 GeneProduct ncbigene:9064
MAP3K8 GeneProduct ncbigene:1326
NGF GeneProduct ensembl:ENSG00000134259
CRKL GeneProduct ncbigene:1399
TAOK2 GeneProduct ncbigene:9344
MAPK3 GeneProduct ncbigene:5595
MAPK8 GeneProduct ncbigene:5599
NR4A1 GeneProduct ncbigene:3164
PRKCA GeneProduct ensembl:ENSG00000154229
ATF4 GeneProduct ncbigene:468
NTF4 GeneProduct ensembl:ENSG00000225950
PDGFA GeneProduct ensembl:ENSG00000197461
ATF4 GeneProduct ncbigene:468
NTRK2 GeneProduct ensembl:ENSG00000148053
FASLG GeneProduct ncbigene:356
PDGFRB GeneProduct ensembl:ENSG00000113721
PPM1B GeneProduct ncbigene:5495
FGFR2 GeneProduct ensembl:ENSG00000066468
CDC42 GeneProduct ncbigene:998
FGFR3 GeneProduct ensembl:ENSG00000068078
MP1 GeneProduct ncbigene:8649
FGFR4 GeneProduct ensembl:ENSG00000160867
JUN GeneProduct ncbigene:3725
SOS1 GeneProduct ensembl:ENSG00000115904
JUND GeneProduct ncbigene:3727
RRAS GeneProduct ensembl:ENSG00000126458
HRAS GeneProduct ensembl:ENSG00000174775
RPS6KA5 GeneProduct ncbigene:9252
MAP3K12 GeneProduct ncbigene:7786
TP53 GeneProduct ncbigene:7157
RRAS2 GeneProduct ensembl:ENSG00000133818
NFKB1 GeneProduct ncbigene:4790
GNG12 GeneProduct ensembl:ENSG00000172380
PLA2G4C GeneProduct ensembl:ENSG00000105499
NF1 GeneProduct ensembl:ENSG00000196712
RASGRP2 GeneProduct ensembl:ENSG00000068831
AKT1 GeneProduct ncbigene:207
RASGRP3 GeneProduct ensembl:ENSG00000152689
RASGRP4 GeneProduct ensembl:ENSG00000171777
RASA1 GeneProduct ncbigene:5921
RASGRF1 GeneProduct ensembl:ENSG00000058335
HSPA6 GeneProduct ensembl:ENSG00000173110
NTF3 GeneProduct ensembl:ENSG00000185652
RAPGEF2 GeneProduct ensembl:ENSG00000109756
PRKACB GeneProduct ensembl:ENSG00000142875
HSPA1A GeneProduct ncbigene:3303
PRKACG GeneProduct ensembl:ENSG00000165059
STK3 GeneProduct ncbigene:6788
DUSP3 GeneProduct ensembl:ENSG00000108861
MAP4K3 GeneProduct ncbigene:8491
CHUK GeneProduct ensembl:ENSG00000213341
TGFBR2 GeneProduct ncbigene:7048
NFKB2 GeneProduct ensembl:ENSG00000077150
MAP4K2 GeneProduct ensembl:ENSG00000168067
RELA GeneProduct ensembl:ENSG00000173039
MAP2K7 GeneProduct ncbigene:5609
RELB GeneProduct ensembl:ENSG00000104856
PPP3R1 GeneProduct ncbigene:5534
DUSP9 GeneProduct ensembl:ENSG00000130829
NLK GeneProduct ncbigene:51701
DUSP2 GeneProduct ensembl:ENSG00000158050
DUSP16 GeneProduct ensembl:ENSG00000111266
FAS GeneProduct ncbigene:355
MKNK2 GeneProduct ensembl:ENSG00000099875
PLA2G4A GeneProduct ensembl:ENSG00000116711
NFATC3 GeneProduct ensembl:ENSG00000072736
MAP3K5 GeneProduct ncbigene:4217
MAP3K11 GeneProduct ncbigene:4296
TAOK3 GeneProduct ensembl:ENSG00000135090
DUSP6 GeneProduct ncbigene:1848
MAP2K2 GeneProduct ncbigene:5605
PPP5D1 GeneProduct ensembl:ENSG00000230510
MAPK11 GeneProduct ensembl:ENSG00000185386
RPS6KA4 GeneProduct ensembl:ENSG00000162302
MAPKAPK3 GeneProduct ensembl:ENSG00000114738
RAC3 GeneProduct ensembl:ENSG00000169750
MAPK8IP2 GeneProduct ensembl:ENSG00000008735
MAPK8IP3 GeneProduct ensembl:ENSG00000138834
FLNB GeneProduct ensembl:ENSG00000136068
FLNC GeneProduct ensembl:ENSG00000128591
HSPA1B GeneProduct ensembl:ENSG00000204388
HSPA1L GeneProduct ensembl:ENSG00000204390
HSPA2 GeneProduct ensembl:ENSG00000126803
MRAS GeneProduct ncbigene:22808
NRAS GeneProduct ncbigene:4893
KRAS GeneProduct ncbigene:3845
RAF1 GeneProduct ncbigene:5894
PLA2G4F GeneProduct ensembl:ENSG00000168907
PLA2G4B GeneProduct ensembl:ENSG00000243708
PLA2G4E GeneProduct ensembl:ENSG00000188089
CACNG2 GeneProduct ensembl:ENSG00000166862
CACNG5 GeneProduct ensembl:ENSG00000075429
CACNG4 GeneProduct ensembl:ENSG00000075461
CACNA2D3 GeneProduct ensembl:ENSG00000157445
CACNG8 GeneProduct ensembl:ENSG00000142408
CACNG7 GeneProduct ensembl:ENSG00000105605
CACNG6 GeneProduct ensembl:ENSG00000130433
CACNA1A GeneProduct ensembl:ENSG00000141837
CACNA1B GeneProduct ensembl:ENSG00000148408
CACNA1C GeneProduct ensembl:ENSG00000151067
CACNA1D GeneProduct ensembl:ENSG00000157388
CACNA1E GeneProduct ensembl:ENSG00000198216
CACNA1F GeneProduct ensembl:ENSG00000102001
CACNA1S GeneProduct ensembl:ENSG00000081248
CACNA2D1 GeneProduct ensembl:ENSG00000153956
CACNB1 GeneProduct ensembl:ENSG00000067191
CACNB2 GeneProduct ensembl:ENSG00000165995
CACNB3 GeneProduct ensembl:ENSG00000167535
CACNB4 GeneProduct ensembl:ENSG00000182389
CACNG1 GeneProduct ensembl:ENSG00000108878
CACNA1I GeneProduct ensembl:ENSG00000100346
CACNA1H GeneProduct ensembl:ENSG00000196557
CACNA1G GeneProduct ensembl:ENSG00000006283
CACNA2D2 GeneProduct ensembl:ENSG00000007402
CACNA2D4 GeneProduct ensembl:ENSG00000151062
FGF4 GeneProduct ncbigene:2249
FGF1 GeneProduct ensembl:ENSG00000113578
FGF2 GeneProduct ensembl:ENSG00000138685
FGF3 GeneProduct ensembl:ENSG00000186895
FGF4 GeneProduct ensembl:ENSG00000075388
FGF5 GeneProduct ensembl:ENSG00000138675
FGF6 GeneProduct ensembl:ENSG00000111241
FGF7 GeneProduct ensembl:ENSG00000140285
FGF8 GeneProduct ensembl:ENSG00000107831
FGF9 GeneProduct ensembl:ENSG00000102678
FGF10 GeneProduct ensembl:ENSG00000070193
FGF11 GeneProduct ensembl:ENSG00000161958
FGF12 GeneProduct ensembl:ENSG00000114279
FGF13 GeneProduct ensembl:ENSG00000129682
FGF14 GeneProduct ensembl:ENSG00000102466
FGF20 GeneProduct ensembl:ENSG00000078579
FGF21 GeneProduct ensembl:ENSG00000105550
FGF22 GeneProduct ensembl:ENSG00000070388
FGF23 GeneProduct ensembl:ENSG00000118972
FGF18 GeneProduct ensembl:ENSG00000156427
FGF17 GeneProduct ensembl:ENSG00000158815
FGF16 GeneProduct ensembl:ENSG00000196468
FGF19 GeneProduct ensembl:ENSG00000162344
PAK2 GeneProduct ncbigene:5062
PAK1 GeneProduct ncbigene:5058

References

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  2. 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
  3. 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
  4. 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
  5. The role of mitogen-activated protein kinase pathways in Alzheimer’s disease. Zhu X, Lee H gon, Raina AK, Perry G, Smith MA. Neurosignals. 2002;11(5):270–81. PubMed Europe PMC Scholia
  6. Trk receptors: roles in neuronal signal transduction. Huang EJ, Reichardt LF. Annu Rev Biochem. 2003;72:609–42. PubMed Europe PMC Scholia
  7. 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
  8. MAPK pathways in radiation responses. Dent P, Yacoub A, Fisher PB, Hagan MP, Grant S. Oncogene. 2003 Sep 1;22(37):5885–96. PubMed Europe PMC Scholia
  9. 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
  10. 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
  11. (G2019S) LRRK2 activates MKK4-JNK pathway and causes degeneration of SN dopaminergic neurons in a transgenic mouse model of PD. Chen CY, Weng YH, Chien KY, Lin KJ, Yeh TH, Cheng YP, et al. Cell Death Differ. 2012 Oct;19(10):1623–33. PubMed Europe PMC Scholia