KEGG   PATHWAY: ko04010Help
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
BRITE hierarchy
Pathway map
MAPK signaling pathway
ko04010

All organismsOrtholog table
Disease
H00078  
Frontotemporal lobar degeneration (FTLD)
H00265  
Hereditary sensory and autonomic neuropathy (HSAN)
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  
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
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 subunit A
K17386  
platelet-derived growth factor subunit 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  
mitogen-activated protein kinase 1/3 [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 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]
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  
M-phase inducer phosphatase 2 [EC:3.1.3.48]
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
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 [EC:3.1.3.16]
K04458  
receptor-type tyrosine-protein phosphatase R [EC:3.1.3.48]
K18018  
tyrosine-protein phosphatase non-receptor type 5 [EC:3.1.3.48]
K18019  
tyrosine-protein phosphatase non-receptor type 7 [EC:3.1.3.48]
K04459  
dual specificity MAP kinase phosphatase [EC:3.1.3.48 3.1.3.16]
K17614  
dual specificity phosphatase 3 [EC:3.1.3.48 3.1.3.16]
K04460  
serine/threonine-protein phosphatase 5 [EC:3.1.3.16]
K04461  
protein phosphatase 1B [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
  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
  Authors
Tanoue T, Nishida E.
  Title
Docking interactions in the mitogen-activated protein kinase cascades.
  Journal
Pharmacol Ther 93:193-202 (2002)
Reference
  Authors
Dent P, Yacoub A, Fisher PB, Hagan MP, Grant S.
  Title
MAPK pathways in radiation responses.
  Journal
Oncogene 22:5885-96 (2003)
Reference
  Authors
Huang EJ, Reichardt LF.
  Title
Trk receptors: roles in neuronal signal transduction.
  Journal
Annu Rev Biochem 72:609-42 (2003)
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)
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)
Reference
  Authors
Yang SH, Sharrocks AD, Whitmarsh AJ.
  Title
Transcriptional regulation by the MAP kinase signaling cascades.
  Journal
Gene 320:3-21 (2003)
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)
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)

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