KEGG PATHWAY: ko04010

PATHWAY: ko04010

Entry

ko04010 Pathway

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

Pathway map

ko04010

MAPK signaling pathway

Disease

H00078	Frontotemporal lobar degeneration (FTLD)
H00484	Other brachydactylies
H00523	Noonan syndrome and related disorders
H00532	RASA1-related disorders
H00539	PTEN hamartoma tumor syndrome (PHTS)
H00540	Osteoporosis, lymphedema, anhydrotic ectodermal dysplasia with immunodeficiency (OLEDAID)
H00574	Coffin-Lowry syndrome (CLS)
H00577	Syndromic X-linked mental retardation with epilepsy or seizures
H00595	Myofibrillar myopathies (MFM)
H00642	Lacrimo-auriculo-dento-digital syndrome (LADD)
H00645	Incontinentia pigmenti
H00677	Aplasia of lacrimal and salivary glands
H00728	Brugada syndrome (BRS)
H00746	Hypokalemic periodic paralysis (HypoPP)
H00749	Episodic ataxias
H00775	Familial or sporadic hemiplegic migraine
H00787	Congenital stationary night blindness (CSNB)
H00800	Loeys-Dietz syndrome (LDS)
H00801	Familial thoracic aortic aneurysm and dissection (TAAD)
H00808	Idiopathic generalized epilepsies (IGEs)
H00856	Distal hereditary motor neuropathies (dHMN)
H00881	Li-Fraumeni syndrome
H00882	Cocoon syndrome
H00894	FG syndrome (FGS)
H00912	Tumor necrosis factor receptor-associated periodic syndrome (TRAPS)
H00916	Congenital central hypoventilation syndrome (CCHS)
H00997	CATSHL syndrome
H01007	Choroid plexus papilloma
H01193	Familial tumoral calcinosis (FTC)
H01207	Trigonocephaly
H01250	Hereditary gingival fibromatosis (HGF)
H01276	X-linked chronic idiopathic intestinal pseudo-obstruction

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
K05315	voltage-dependent calcium channel alpha 1, invertebrate
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
K05316	voltage-dependent calcium channel alpha-2/delta, invertebrate
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
K05317	voltage-dependent calcium channel beta, invertebrate
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
K04345	protein kinase A [EC:2.7.11.11]
K02677	classical protein kinase C [EC:2.7.11.13]
K04346	guanine nucleotide-binding protein subunit alpha-12
K04347	guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-12
K04348	protein phosphatase 3, catalytic subunit [EC:3.1.3.16]
K06268	protein phosphatase 3, 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 (GEF) 2
K08052	neurofibromin 1
K04352	Ras GTPase-activating protein 1
K08053	Ras GTPase-activating protein 2
K04353	Ras-related protein Rap-1A
K07836	Ras-related protein Rap-1B
K02582	nerve growth factor, beta
K04355	brain-derived neurotrophic factor
K04356	neurotrophin 3
K12457	neurotrophin 4
K04357	epidermal growth factor
K04358	fibroblast growth factor
K04359	platelet derived growth factor A/B
K03176	neurotrophic tyrosine kinase receptor type 1 [EC:2.7.10.1]
K04360	neurotrophic tyrosine kinase receptor type 2 [EC:2.7.10.1]
K04361	epidermal growth factor receptor [EC:2.7.10.1]
K04362	fibroblast growth factor receptor 1 [EC:2.7.10.1]
K05093	fibroblast growth factor receptor 2 [EC:2.7.10.1]
K05094	fibroblast growth factor receptor 3 [EC:2.7.10.1]
K05095	fibroblast growth factor receptor 4 [EC:2.7.10.1]
K04363	platelet-derived growth factor receptor alpha [EC:2.7.10.1]
K05089	platelet-derived growth factor receptor beta [EC:2.7.10.1]
K04364	growth factor receptor-binding protein 2
K03099	son of sevenless
K02833	GTPase HRas
K07827	GTPase KRas
K07828	GTPase NRas
K07829	Ras-related protein R-Ras
K07830	Ras-related protein R-Ras2
K07831	Ras-related protein M-Ras
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]
K04367	proto-oncogene serine/threonine-protein kinase mos [EC:2.7.11.1]
K04368	mitogen-activated protein kinase kinase 1 [EC:2.7.12.2]
K04369	mitogen-activated protein kinase kinase 2 [EC:2.7.12.2]
K04370	mitogen-activated protein kinase kinase 1 interacting protein 1
K04371	extracellular signal-regulated kinase 1/2 [EC:2.7.11.24]
K04372	MAP kinase interacting serine/threonine kinase [EC:2.7.11.1]
K04373	p90 ribosomal S6 kinase [EC:2.7.11.1]
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
K04378	serum response factor
K04379	proto-oncogene protein c-fos
K04380	microtubule-associated protein tau
K04381	stathmin
K16342	cytosolic phospholipase A2 [EC:3.1.1.4]
K03156	tumor necrosis factor superfamily, member 2
K04383	interleukin 1 alpha
K04519	interleukin 1 beta
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
K04387	interleukin 1 receptor type II
K04674	TGF-beta receptor type-1 [EC:2.7.11.30]
K04388	TGF-beta receptor type-2 [EC:2.7.11.30]
K04389	tumor necrosis factor ligand superfamily member 6
K04390	tumor necrosis factor receptor superfamily member 6
K04391	CD14 antigen
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
K02187	caspase 3 [EC:3.4.22.56]
K03173	TNF receptor-associated factor 2
K02308	death-associated protein 6
K03175	TNF receptor-associated factor 6
K04402	growth arrest and DNA-damage-inducible protein
K04403	TAK1-binding protein 1
K04404	TAK1-binding protein 2
K04405	evolutionarily conserved signaling intermediate in Toll pathways
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]
K04409	p21-activated kinase 1 [EC:2.7.11.1]
K04410	p21-activated kinase 2 [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]
K04415	mitogen-activated protein kinase kinase kinase 8 [EC:2.7.11.25]
K04416	mitogen-activated protein kinase kinase kinase 1 [EC:2.7.11.25]
K04419	mitogen-activated protein kinase kinase kinase 11 [EC:2.7.11.25]
K04420	mitogen-activated protein kinase kinase kinase 2 [EC:2.7.11.25]
K04421	mitogen-activated protein kinase kinase kinase 3 [EC:2.7.11.25]
K04422	mitogen-activated protein kinase kinase kinase 13 [EC:2.7.11.25]
K04423	mitogen-activated protein kinase kinase kinase 12 [EC:2.7.11.25]
K04424	sterile alpha motif and leucine zipper containing kinase AZK [EC:2.7.11.25]
K04425	mitogen-activated protein kinase kinase kinase 6 [EC:2.7.11.25]
K04426	mitogen-activated protein kinase kinase kinase 5 [EC:2.7.11.25]
K04427	mitogen-activated protein kinase kinase kinase 7 [EC:2.7.11.25]
K04428	mitogen-activated protein kinase kinase kinase 4 [EC:2.7.11.25]
K04429	thousand and one amino acid protein kinase [EC:2.7.11.1]
K04430	mitogen-activated protein kinase kinase 4 [EC:2.7.12.2]
K04431	mitogen-activated protein kinase kinase 7 [EC:2.7.12.2]
K04432	mitogen-activated protein kinase kinase 3 [EC:2.7.12.2]
K04433	mitogen-activated protein kinase kinase 6 [EC:2.7.12.2]
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
K04437	filamin
K04438	proto-oncogene C-crk
K04439	beta-arrestin
K04440	c-Jun N-terminal kinase [EC:2.7.11.24]
K04441	p38 MAP 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]
K04445	ribosomal protein S6 kinase alpha-5 [EC:2.7.11.1]
K16510	ribosomal protein S6 kinase alpha-4 [EC:2.7.11.1]
K05866	cell division cycle 25B [EC:3.1.3.48]
K04448	transcription factor AP-1
K04449	transcription factor jun-D
K04450	cyclic AMP-dependent transcription factor ATF-2
K04451	tumor protein p53
K04452	DNA damage-inducible transcript 3
K04453	Max protein
K04454	MADS-box transcription enhancer factor 2C
K04455	heat shock protein beta-1
K04456	RAC serine/threonine-protein kinase [EC:2.7.11.1]
K04457	protein phosphatase 1A (formerly 2C) [EC:3.1.3.16]
K04458	protein-tyrosine phosphatase [EC:3.1.3.48]
K04459	dual specificity phosphatase [EC:3.1.3.48 3.1.3.16]
K04460	protein phosphatase 5 [EC:3.1.3.16]
K04461	protein phosphatase 1B (formerly 2C) [EC:3.1.3.16]
K03283	heat shock 70kDa protein 1/8
K04462	ecotropic virus integration site 1 protein
K04463	mitogen-activated protein kinase kinase 5 [EC:2.7.12.2]
K04464	mitogen-activated protein kinase 7 [EC:2.7.11.24]
K04465	nuclear receptor subfamily 4 group A member 1
K04466	mitogen-activated protein kinase kinase kinase 14 [EC:2.7.11.25]
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
K04468	nemo like kinase [EC:2.7.11.24]
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

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)

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)

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)

Reference

PMID:12676795

Authors

Huang EJ, Reichardt LF.

Title

Trk receptors: roles in neuronal signal transduction.

Journal

Annu Rev Biochem 72:609-42 (2003)

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)

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)

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)

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)

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)

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Ontology (1)   
   KEGG BRITE (1)   
Pathway (2)   
   KEGG PATHWAY (1)   
   BioSystems (1)   
Disease (32)   
   KEGG DISEASE (32)   
Chemical substance (5)   
   KEGG COMPOUND (5)   
Chemical reaction (13)   
   KEGG ENZYME (13)   
Gene (182)   
   KEGG ORTHOLOGY (182)   
Literature (9)   
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