KEGG   PATHWAY: map04010Help
Entry
map04010                    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
09130 Environmental Information Processing; 09132 Signal transduction
BRITE hierarchy
Pathway map
map04010  MAPK signaling pathway
map04010

Ortholog table
Module
M00687  MAPK (ERK1/2) signaling [PATH:map04010]
M00688  MAPK (JNK) signaling [PATH:map04010]
M00689  MAPK (p38) signaling [PATH:map04010]
M00690  MAPK (ERK5) signaling [PATH:map04010]
Disease
H00078  Frontotemporal lobar degeneration (FTLD)
H00265  Hereditary sensory and autonomic neuropathy (HSAN)
H00484  Multiple synostosis syndrome
H00505  FGFR3-related short limb skeletal dysplasia
H00523  Noonan syndrome and related disorders
H00532  Parkes Weber syndrome
H00540  Osteoporosis, lymphedema, anhydrotic ectodermal dysplasia with immunodeficiency (OLEDAID)
H00574  Coffin-Lowry syndrome (CLS)
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)
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  Chronic idiopathic intestinal pseudo-obstruction
H01385  Rienhoff syndrome
H01437  Neurofibromatosis type 1
H01512  Langerhans cell histiocytosis
H01738  Noonan syndrome
H01745  Cardiofaciocutaneous syndrome
H01905  Trichomegaly
H01984  Leopard syndrome
H02043  Capillary malformation-arteriovenous malformation
H02064  Atelosteogenesis type I and III
H02067  Boomerang dysplasia
H02068  Hypochondroplasia
H02069  SADDAN
Other DBs
GO: 0000165
Reference
  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)
DOI:10.1021/cr000241p
Reference
  Authors
Tanoue T, Nishida E.
  Title
Docking interactions in the mitogen-activated protein kinase cascades.
  Journal
Pharmacol Ther 93:193-202 (2002)
DOI:10.1016/S0163-7258(02)00188-2
Reference
  Authors
Dent P, Yacoub A, Fisher PB, Hagan MP, Grant S.
  Title
MAPK pathways in radiation responses.
  Journal
Oncogene 22:5885-96 (2003)
DOI:10.1038/sj.onc.1206701
Reference
  Authors
Huang EJ, Reichardt LF.
  Title
Trk receptors: roles in neuronal signal transduction.
  Journal
Annu Rev Biochem 72:609-42 (2003)
DOI:10.1146/annurev.biochem.72.121801.161629
Reference
  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)
DOI:10.1016/S0898-6568(01)00148-6
Reference
  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)
DOI:10.1046/j.1365-2443.2002.00591.x
Reference
  Authors
Yang SH, Sharrocks AD, Whitmarsh AJ.
  Title
Transcriptional regulation by the MAP kinase signaling cascades.
  Journal
Gene 320:3-21 (2003)
DOI:10.1016/S0378-1119(03)00816-3
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
Neurosignals 11:270-81 (2002)
DOI:10.1159/000067426
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
Toxicol Lett 143:323-30 (2003)
DOI:10.1016/S0378-4274(03)00193-0
Reference
  Authors
Lemmon MA, Schlessinger J
  Title
Cell signaling by receptor tyrosine kinases.
  Journal
Cell 141:1117-34 (2010)
DOI:10.1016/j.cell.2010.06.011
Reference
  Authors
Skaper SD
  Title
The neurotrophin family of neurotrophic factors: an overview.
  Journal
Methods Mol Biol 846:1-12 (2012)
DOI:10.1007/978-1-61779-536-7_1
Reference
  Authors
Chu WM
  Title
Tumor necrosis factor.
  Journal
Cancer Lett 328:222-5 (2013)
DOI:10.1016/j.canlet.2012.10.014
Reference
  Authors
Newton K, Dixit VM
  Title
Signaling in innate immunity and inflammation.
  Journal
Cold Spring Harb Perspect Biol 4:a006049 (2012)
DOI:10.1101/cshperspect.a006049
Reference
  Authors
Gaestel M, Kotlyarov A, Kracht M
  Title
Targeting innate immunity protein kinase signalling in inflammation.
  Journal
Nat Rev Drug Discov 8:480-99 (2009)
DOI:10.1038/nrd2829
Reference
  Authors
Ajibade AA, Wang HY, Wang RF
  Title
Cell type-specific function of TAK1 in innate immune signaling.
  Journal
Trends Immunol 34:307-16 (2013)
DOI:10.1016/j.it.2013.03.007
Reference
  Authors
Turner MD, Nedjai B, Hurst T, Pennington DJ
  Title
Cytokines and chemokines: At the crossroads of cell signalling and inflammatory disease.
  Journal
Biochim Biophys Acta 1843:2563-2582 (2014)
DOI:10.1016/j.bbamcr.2014.05.014
KO pathway
ko04010   

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