Entry
Name
MAPK signaling pathway
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
Orthology
K04344 voltage-dependent calcium channel P/Q type alpha-1A
K04849 voltage-dependent calcium channel N type alpha-1B
K04850 voltage-dependent calcium channel L type alpha-1C
K04851 voltage-dependent calcium channel L type alpha-1D
K04852 voltage-dependent calcium channel R type alpha-1E
K04853 voltage-dependent calcium channel L type alpha-1F
K04854 voltage-dependent calcium channel T type alpha-1G
K04855 voltage-dependent calcium channel T type alpha-1H
K04856 voltage-dependent calcium channel T type alpha-1I
K04857 voltage-dependent calcium channel L type alpha-1S
K04858 voltage-dependent calcium channel alpha-2/delta-1
K04859 voltage-dependent calcium channel alpha-2/delta-2
K04860 voltage-dependent calcium channel alpha-2/delta-3
K04861 voltage-dependent calcium channel alpha-2/delta-4
K04862 voltage-dependent calcium channel beta-1
K04863 voltage-dependent calcium channel beta-2
K04864 voltage-dependent calcium channel beta-3
K04865 voltage-dependent calcium channel beta-4
K04866 voltage-dependent calcium channel gamma-1
K04867 voltage-dependent calcium channel gamma-2
K04868 voltage-dependent calcium channel gamma-3
K04869 voltage-dependent calcium channel gamma-4
K04870 voltage-dependent calcium channel gamma-5
K04871 voltage-dependent calcium channel gamma-6
K04872 voltage-dependent calcium channel gamma-7
K04873 voltage-dependent calcium channel gamma-8
K04346 guanine nucleotide-binding protein subunit alpha-12
K04347 guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-12
K04348 serine/threonine-protein phosphatase 2B catalytic subunit [EC:3.1.3.16 ]
K06268 serine/threonine-protein phosphatase 2B regulatory subunit
K04349 Ras-specific guanine nucleotide-releasing factor 1
K12326 Ras-specific guanine nucleotide-releasing factor 2
K04350 RAS guanyl-releasing protein 1
K12361 RAS guanyl-releasing protein 2
K12362 RAS guanyl-releasing protein 3
K12363 RAS guanyl-releasing protein 4
K08018 Rap guanine nucleotide exchange factor 2
K04352 Ras GTPase-activating protein 1
K08053 Ras GTPase-activating protein 2
K04353 Ras-related protein Rap-1A
K07836 Ras-related protein Rap-1B
K04357 epidermal growth factor
K08774 transforming growth factor, alpha
K18496 fibroblast growth factor 1
K18497 fibroblast growth factor 2
K04358 fibroblast growth factor
K22603 fibroblast growth factor 19
K22429 fibroblast growth factor 21
K22428 fibroblast growth factor 23
K05451 nerve growth factor, alpha
K02582 nerve growth factor, beta
K04355 brain-derived neurotrophic factor
K05459 insulin-like growth factor 1
K13769 insulin-like growth factor 2
K04359 platelet-derived growth factor subunit A
K17386 platelet-derived growth factor subunit B
K05450 platelet derived growth factor C/D
K05453 macrophage colony-stimulating factor 1
K05454 fms-related tyrosine kinase 3 ligand
K05448 vascular endothelial growth factor A
K16858 vascular endothelial growth factor B
K05449 vascular endothelial growth factor C/D
K05460 hepatocyte growth factor
K05452 glial cell derived neurotrophic factor
K02583 tumor necrosis factor receptor superfamily member 16
K04364 growth factor receptor-bound protein 2
K07829 Ras-related protein R-Ras
K07830 Ras-related protein R-Ras2
K07831 Ras-related protein M-Ras
K08845 A-Raf proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1 ]
K04365 B-Raf proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1 ]
K04366 RAF proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1 ]
K04370 ragulator complex protein LAMTOR3
K04374 cyclic AMP-dependent transcription factor ATF-4
K04375 ETS domain-containing protein Elk-1
K04376 ETS domain-containing protein Elk-4
K04377 Myc proto-oncogene protein
K04379 proto-oncogene protein c-fos
K04380 microtubule-associated protein tau
K03156 tumor necrosis factor superfamily, member 2
K13375 transforming growth factor beta-1
K13376 transforming growth factor beta-2
K13377 transforming growth factor beta-3
K03158 tumor necrosis factor receptor superfamily member 1A
K04386 interleukin 1 receptor type I
K04723 interleukin 1 receptor accessory protein
K04389 tumor necrosis factor ligand superfamily member 6
K04390 tumor necrosis factor receptor superfamily member 6
K04391 monocyte differentiation antigen CD14
K04392 Ras-related C3 botulinum toxin substrate 1
K07860 Ras-related C3 botulinum toxin substrate 2
K07861 Ras-related C3 botulinum toxin substrate 3
K04393 cell division control protein 42
K03171 tumor necrosis factor receptor type 1-associated DEATH domain protein
K02308 death-associated protein 6
K04729 myeloid differentiation primary response protein MyD88
K04402 growth arrest and DNA-damage-inducible protein
K04405 evolutionarily conserved signaling intermediate in Toll pathway
K04406 mitogen-activated protein kinase kinase kinase kinase 3 [EC:2.7.11.1 ]
K04407 mitogen-activated protein kinase kinase kinase kinase 4 [EC:2.7.11.1 ]
K04408 mitogen-activated protein kinase kinase kinase kinase 1 [EC:2.7.11.1 ]
K04411 serine/threonine kinase 4
K04412 serine/threonine kinase 3
K04414 mitogen-activated protein kinase kinase kinase kinase 2 [EC:2.7.11.1 ]
K04424 sterile alpha motif and leucine zipper containing kinase AZK [EC:2.7.11.25 ]
K04434 mitogen-activated protein kinase 8 interacting protein 1
K04435 mitogen-activated protein kinase 8 interacting protein 2
K04436 mitogen-activated protein kinase 8 interacting protein 3
K04438 C-crk adapter molecule crk
K04440 mitogen-activated protein kinase 8/9/10 (c-Jun N-terminal kinase) [EC:2.7.11.24 ]
K04442 mitogen-activated protein kinase-activated protein kinase 5 [EC:2.7.11.1 ]
K04443 mitogen-activated protein kinase-activated protein kinase 2 [EC:2.7.11.1 ]
K04444 mitogen-activated protein kinase-activated protein kinase 3 [EC:2.7.11.1 ]
K04446 nuclear factor of activated T-cells, cytoplasmic 1
K17333 nuclear factor of activated T-cells, cytoplasmic 3
K04448 transcription factor AP-1
K04449 transcription factor jun-D
K04450 cyclic AMP-dependent transcription factor ATF-2
K04452 DNA damage-inducible transcript 3
K04454 MADS-box transcription enhancer factor 2C
K04455 heat shock protein beta-1
K03283 heat shock 70kDa protein 1/6/8
K04462 [histone H3]-lysine9 N-methyltransferase (ecotropic virus integration site 1 protein) [EC:2.1.1.367 ]
K04465 nuclear receptor subfamily 4 group A member 1
K04467 inhibitor of nuclear factor kappa-B kinase subunit alpha [EC:2.7.11.10 ]
K07209 inhibitor of nuclear factor kappa-B kinase subunit beta [EC:2.7.11.10 ]
K07210 inhibitor of nuclear factor kappa-B kinase subunit gamma
K02580 nuclear factor NF-kappa-B p105 subunit
K04469 nuclear factor of kappa light polypeptide gene enhancer in B-cells 2
K04735 transcription factor p65
K09253 transcription factor RelB
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
ko04070 Phosphatidylinositol signaling system
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