C-JUN N-TERMINAL KINASES MAPK SIGNALING PATHWAY (PW:0000313)

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Description

The c-Jun N-terminal kinase pathway (Jnk), known as a stress activated protein kinase pathway (SAPK), responds to inflammatory cytokines and various stresses and to a lesser degree to growth factors. Jnk displays the characteristic three-tier core cascade MAPK architecture. The downstream and effector MAPK tier (here Jnk1-3 represented by Mapk8-10) is activated by phosphorylation of threonine and tyrosine residues within the conserved TPY motif in the activation loop by dual specificity k

Pathway Diagram:

Elsevier Inc. upstream c-Jun other upstream c-Jun Rac1 --+> Map3k4 Rac1 --+> Map3k1 Rac1 --+> Map3k11 Cdc42 --+> Map3k4 Map3k4 Cdc42 --+> Map3k1 Cdc42 --+> Map3k11 effectors/adapters --+> Cdc42 effectors/adapters --+> Rac1 stress conditions --+> Map3k5 Mapk10 Mapk9 Mapk8 Map2k7 Map2k4 Map3k5 --+> Map2k4 Map3k5 Traf2 Cdc42 Rac1 Map3k11 Map3k1 other Jnk Map3k Jnk scaffolds ---- Map2k4 adapters ---- Traf2 adapters ---- other upstream c-Jun Mapk9 ---> Jnk cytoplasmic/other targets Mapk9 ---> Jnk nuclear targets Map2k7 --+> Mapk8 Map2k4 --+> Mapk9 effectors/adapters ---- upstream c-Jun effectors/adapters stress conditions adapters Traf2 --+> Map3k5 Map2k7 --+> Mapk9 Map2k4 --+> Mapk8 Jnk scaffolds ---- Mapk8 Map3k11 --+> Map2k4 Map3k4 --+> Map2k4 Map3k1 --+> Map2k4 Map3k4 --+> Map2k7 Jnk scaffolds ---- other Jnk Map3k Mapk8 ---> Jnk cytoplasmic/other targets Jnk Dusp members ---| Mapk8 Jnk Dusp members ---| Mapk9 Map3k11 --+> Map2k7 Mapk8 ---> Jnk nuclear targets Jnk scaffolds Jnk Dusp members Jnk nuclear targets Jnk cytoplasmic/other targets other Jnk Map3k ---> Map2k4 other Jnk Map3k --+> Map2k7 Map3k5 --+> Map2k7 Map3k1 --+> Map2k7
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Genes in Pathway:

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c-Jun N-terminal kinases MAPK signaling pathway term browser
Symbol Object Name JBrowse Chr Start Stop Reference
G Cdc42 cell division cycle 42 JBrowse link 5 155,690,267 155,728,385 RGD:2293876
RGD:2293879
G Dusp1 dual specificity phosphatase 1 JBrowse link 10 16,970,642 16,973,425 RGD:2293881
G Dusp10 dual specificity phosphatase 10 JBrowse link 13 104,284,660 104,321,455 RGD:2293881
G Dusp16 dual specificity phosphatase 16 JBrowse link 4 168,470,141 168,551,346 RGD:2293881
G Dusp19 dual specificity phosphatase 19 JBrowse link 3 67,849,966 67,862,475 RGD:2314491
G Dusp8 dual specificity phosphatase 8 JBrowse link 1 215,030,429 215,043,111 RGD:2293881
G Map2k4 mitogen activated protein kinase kinase 4 JBrowse link 10 52,196,121 52,301,887 RGD:2293875
RGD:2298708
RGD:2298577
RGD:2298561
G Map2k7 mitogen activated protein kinase kinase 7 JBrowse link 12 2,546,278 2,555,310 RGD:2293875
RGD:2298577
RGD:2298567
RGD:2298561
G Map3k1 mitogen-activated protein kinase kinase kinase 1 JBrowse link 2 43,329,516 43,393,203 RGD:2293879
RGD:2293875
G Map3k10 mitogen activated protein kinase kinase kinase 10 JBrowse link 1 84,473,178 84,491,689 RGD:2293875
G Map3k11 mitogen-activated protein kinase kinase kinase 11 JBrowse link 1 221,043,119 221,056,420 RGD:2293876
RGD:2298577
RGD:2298567
RGD:2293875
G Map3k12 mitogen activated protein kinase kinase kinase 12 JBrowse link 7 144,102,275 144,120,306 RGD:2293875
G Map3k2 mitogen activated protein kinase kinase kinase 2 JBrowse link 18 24,961,250 25,025,488 RGD:2293879
RGD:2293875
G Map3k3 mitogen activated protein kinase kinase kinase 3 JBrowse link 10 94,280,703 94,349,372 RGD:2293879
RGD:2293875
G Map3k4 mitogen activated protein kinase kinase kinase 4 JBrowse link 1 48,625,714 48,711,642 RGD:2293879
RGD:2293875
G Map3k7 mitogen activated protein kinase kinase kinase 7 JBrowse link 5 47,183,142 47,244,424 RGD:2293875
G Map3k9 mitogen-activated protein kinase kinase kinase 9 JBrowse link 6 105,455,461 105,518,974 RGD:2293875
G Mapk10 mitogen activated protein kinase 10 JBrowse link 14 8,079,955 8,371,508 RGD:2293875
RGD:2298567
RGD:2298561
G Mapk8 mitogen-activated protein kinase 8 JBrowse link 16 9,620,854 9,709,342 RGD:2293875
RGD:2298577
RGD:2298561
G Mapk8ip1 mitogen-activated protein kinase 8 interacting protein 1 JBrowse link 3 81,295,023 81,304,181 RGD:2293880
RGD:1579811
G Mapk8ip2 mitogen-activated protein kinase 8 interacting protein 2 JBrowse link 7 130,430,588 130,440,838 RGD:2293880
G Mapk8ip3 mitogen-activated protein kinase 8 interacting protein 3 JBrowse link 10 14,259,394 14,299,276 RGD:2293880
G Mapk9 mitogen-activated protein kinase 9 JBrowse link 10 35,333,859 35,374,364 RGD:2293875
RGD:2298577
RGD:2298561
G Rac1 ras-related C3 botulinum toxin substrate 1 JBrowse link 12 13,090,316 13,111,841 RGD:2293876
RGD:2293879
G Rapgef1 Rap guanine nucleotide exchange factor 1 JBrowse link 3 8,189,594 8,307,077 RGD:11534984
G Spp1 secreted phosphoprotein 1 JBrowse link 14 6,673,686 6,679,965 RGD:1581337
G Traf2 Tnf receptor-associated factor 2 JBrowse link 3 2,746,061 2,770,690 RGD:2296020

Additional Elements in Pathway:

(includes Gene Groups, Small Molecules, Other Pathways..etc.)
Object TypePathway ObjectPathway Object Description
Gene GroupJnk Dusp membersdual specificity phosphatases for Jnk Mapks
Gene GroupJnk scaffoldsmembers of the Jip family

Pathway Gene Annotations

Disease Annotations Associated with Genes in the c-Jun N-terminal kinases MAPK signaling pathway
Disease TermsGene Symbols
46,XY Sex Reversal 6Map3k1
Abnormalities, MultipleCdc42
Acute Kidney InjurySpp1
AdenocarcinomaSpp1
Adenocarcinoma, ColonRac1
Adenocarcinoma, ColorectalMapk8
Adenoma, ColorectalMapk8
Adrenal Gland NeoplasmsCdc42
AlbuminuriaSpp1
Alzheimer DiseaseCdc42 , Mapk10 , Mapk8 , Mapk9
Amyloid NeuropathiesDusp1
AneurysmSpp1
Angina PectorisSpp1
Anti-Glomerular Basement Membrane DiseaseDusp1 , Mapk8 , Rapgef1 , Spp1
Aortic Aneurysm, AbdominalMapk8
Arrhythmias, CardiacMap2k4
ArteriosclerosisDusp1 , Mapk9
Arthritis, ExperimentalCdc42
Arthritis, JuvenileDusp1
Arthritis, RheumatoidSpp1
AsbestosisSpp1
Autism Spectrum DisorderMapk8ip2
Biliary AtresiaSpp1
Bipolar DisorderCdc42
Brain DeathMap2k4
Brain IschemiaMapk8
Brain NeoplasmsSpp1
Breast NeoplasmsDusp1 , Map2k4 , Map2k7 , Map3k1 , Spp1
CalcinosisSpp1
CarcinomaCdc42
Carcinoma, Ductal, BreastMap2k4
Carcinoma, EndometrioidSpp1
Carcinoma, HepatocellularRac1 , Spp1
Carcinoma, Non-Small-Cell LungSpp1
Carcinoma, Squamous CellDusp1
Carcinoma, Squamous Cell of Head and NeckRac1
CardiomegalyMapk8 , Rac1 , Spp1
Cardiomyopathy, DilatedRac1
Carotid Artery InjuriesDusp1
Cell Transformation, NeoplasticMapk8 , Rac1
Cerebral HemorrhageSpp1
Chemical and Drug Induced Liver InjurySpp1
ColitisDusp1
colon adenomaRac1
Colonic NeoplasmsMapk8 , Mapk9
colorectal cancerRac1
Coronary Artery DiseaseSpp1
Coronary RestenosisSpp1
Depressive Disorder, MajorDusp1
Dermatitis, Allergic ContactSpp1
Dermatitis, AtopicMapk8
Dermatitis, ContactDusp1
Diabetes MellitusRac1
Diabetes Mellitus, ExperimentalDusp1 , Spp1
Diabetes Mellitus, Type 1Dusp1
Diabetes Mellitus, Type 2Mapk8ip1
Diabetic CardiomyopathiesSpp1
Diabetic EncephalopathiesDusp1
Diabetic NephropathiesSpp1
Disease Models, AnimalMapk8 , Mapk9
Drug-Related Side Effects and Adverse ReactionsSpp1
EncephalomyelitisSpp1
Encephalomyelitis, Autoimmune, ExperimentalDusp10
Endometrial NeoplasmsMap3k4
EndometriosisDusp1
Epilepsy, GeneralizedMapk10
Epilepsy, Temporal LobeCdc42
Epileptic Encephalopathy, Lennox-Gastaut TypeMapk10
Esophageal NeoplasmsMap3k3
Fatty LiverMapk8
Fetal Growth RetardationDusp1
FibrosarcomaCdc42
FibrosisMap2k7 , Spp1
Foreign-Body ReactionSpp1
Forney Robinson Pascoe SyndromeMap3k7
Frontometaphyseal DysplasiaMap3k7
Frontometaphyseal Dysplasia 2Map3k7
Genetic Diseases, InbornCdc42
GliomaSpp1
GlomerulonephritisSpp1
GlomerulosclerosisSpp1
Glomerulosclerosis, Focal SegmentalSpp1
Glucose IntoleranceDusp1
Heart DiseasesSpp1
Heart FailureMap2k7 , Rac1
Heart Valve DiseasesSpp1
HepatitisSpp1
Hepatitis C, ChronicSpp1
HIV InfectionsCdc42
Huntington DiseaseDusp1
HyperalgesiaDusp1 , Mapk8 , Mapk9
HypersensitivitySpp1
HypertensionDusp1 , Mapk8
Hypertension, PortalDusp1
Hypertension, RenovascularSpp1
Hypertrophy, Left VentricularDusp1 , Rac1
InflammationDusp10 , Spp1
Intestinal NeoplasmsMapk8
IschemiaMapk9
Ischemic Attack, TransientDusp1 , Dusp16 , Map2k4
Kidney CalculiSpp1
Kidney DiseasesSpp1
Laryngeal NeoplasmsSpp1
LeishmaniasisDusp1
LeukoencephalopathiesSpp1
Liver CirrhosisSpp1
Liver Cirrhosis, ExperimentalDusp16 , Spp1
Liver DiseasesRac1
Liver Diseases, AlcoholicSpp1
Liver Failure, AcuteMapk8
Liver Neoplasms, ExperimentalSpp1
Liver Reperfusion InjuryMapk8
Loeys-Dietz Syndrome 4Dusp10
Lung NeoplasmsMap2k7 , Spp1
MalariaSpp1
Mammary Neoplasms, AnimalCdc42
Mammary Neoplasms, ExperimentalCdc42 , Dusp1 , Map2k7 , Spp1
MelanomaMap3k9 , Rac1 , Spp1
Melanoma, Cutaneous Malignant, Susceptibility To, 1Rac1
Mesangial Proliferative GlomerulonephritisRapgef1
MesotheliomaSpp1
Microphthalmia, Syndromic 1Map3k1
Mitral Regurgitation, Conductive Deafness, and Fusion of Cervical Vertebrae and of Carpal and Tarsal BonesMap3k7
Monoclonal B-Cell LymphocytosisRapgef1
Multiple MyelomaSpp1
Multiple SclerosisSpp1
Myocardial InfarctionSpp1
Myocardial IschemiaDusp1
Myocardial Reperfusion InjuryMapk8 , Mapk9 , Spp1
MyocarditisSpp1
NecrosisCdc42
Neoplasm MetastasisMapk9 , Rac1 , Spp1
NeoplasmsSpp1
Neoplasms, Cystic, Mucinous, and SerousSpp1
Neoplasms, ExperimentalSpp1
Neovascularization, PathologicSpp1
Neuritis, Autoimmune, ExperimentalSpp1
NeuroblastomaMap2k4 , Map2k7
ObesityDusp1
Osseous Heteroplasia, ProgressiveSpp1
OsteolysisSpp1
Otitis MediaDusp1
Ovarian NeoplasmsDusp1 , Map2k4 , Map2k7 , Spp1
Oxygen-Induced RetinopathyMapk8
Pancreatic DiseasesSpp1
Pancreatic NeoplasmsCdc42 , Map2k4 , Spp1
PancreatitisDusp1 , Dusp10
PapillomaMap2k4
Pleural NeoplasmsSpp1
PneumoniaSpp1
Polycystic Kidney, Autosomal DominantSpp1
Polycystic Ovary SyndromeMapk8ip3
Precancerous ConditionsMap2k7 , Mapk8 , Mapk9
prostate cancerMapk10
Prostatic Intraepithelial NeoplasiaMap2k4 , Map2k7
Prostatic NeoplasmsDusp1 , Map2k4 , Map2k7 , Map3k7 , Mapk10 , Spp1
ProteinuriaSpp1
PsoriasisDusp1
Pulmonary Disease, Chronic ObstructiveMap2k4 , Mapk8
Pulmonary FibrosisSpp1
RadiculopathySpp1
Rectal NeoplasmsMapk8
Renal InsufficiencySpp1
Reperfusion InjuryCdc42 , Mapk8 , Mapk8ip3 , Mapk9 , Spp1
Retina Reperfusion InjuryDusp1 , Map2k4
RhinitisCdc42
ScrapieSpp1
SeizuresDusp1 , Spp1
Skin NeoplasmsMap2k4
Sleep DeprivationMap2k4
Smith-Magenis SyndromeMap3k3
Spinal Cord InjuriesCdc42 , Dusp1 , Spp1
Stomach NeoplasmsMapk8 , Spp1
StrokeMapk8
Takenouchi-Kosaki SyndromeCdc42
Thyroid NeoplasmsSpp1
Trauma, Nervous SystemSpp1
Trigeminal NeuralgiaMapk8 , Mapk9
TuberculosisSpp1
UremiaSpp1
Urinary Bladder NeoplasmsDusp1 , Map2k4 , Spp1
Urinary CalculiSpp1
Usher SyndromesDusp10
Uterine NeoplasmsRac1
Vascular System InjuriesSpp1
Wet Macular DegenerationMapk8
Wilms TumorMap3k4
Wounds and InjuriesSpp1
Pathway Annotations Associated with Genes in the c-Jun N-terminal kinases MAPK signaling pathway
Pathway TermsGene Symbols
adenosine signaling pathwayCdc42 , Map2k7 , Map3k1 , Map3k4 , Mapk8
amyotrophic lateral sclerosis disease pathwayRac1
angiotensin II signaling pathway via AT2 receptorDusp1
apoptotic cell death pathwayTraf2
Arf family mediated signaling pathwayRac1
azathioprine pharmacodynamics pathwayRac1
B cell receptor signaling pathwayRac1
Bone morphogenetic proteins signaling pathwayMap3k7
c-Jun N-terminal kinases MAPK signaling pathwayCdc42 , Dusp1 , Dusp10 , Dusp16 , Dusp19 , Dusp8 , Map2k4 , Map2k7 , Map3k1 , Map3k10 , Map3k11 , Map3k12 , Map3k2 , Map3k3 , Map3k4 , Map3k7 , Map3k9 , Mapk10 , Mapk8 , Mapk8ip1 , Mapk8ip2 , Mapk8ip3 , Mapk9 , Rac1 , Rapgef1 , Spp1 , Traf2
cell-extracellular matrix signaling pathwaySpp1
ceramide signaling pathwayCdc42 , Map2k4 , Map3k1 , Mapk10 , Mapk8 , Mapk9 , Rac1 , Traf2
chemokine mediated signaling pathwayCdc42 , Rac1
colorectal cancer pathwayMapk10 , Mapk8 , Mapk9 , Rac1
diabetic nephropathy pathwaySpp1
E-cadherin signaling pathwayCdc42 , Rac1
eicosanoid signaling pathwayRac1
endocytosis pathwayCdc42
Endoplasmic Reticulum-associated degradation pathwayMap2k7 , Mapk10 , Mapk8 , Mapk9 , Traf2
endothelin signaling pathwayCdc42 , Mapk8 , Rac1
ephrin - ephrin receptor bidirectional signaling axisCdc42 , Map2k4 , Map3k7 , Mapk8 , Rac1
epidermal growth factor/neuregulin signaling pathwayMap2k4 , Map2k7 , Mapk10 , Mapk8 , Mapk9
Erk5 MAPK signaling pathwayMap3k2 , Map3k3
erythropoietin signaling pathwayMapk8
FasL mediated signaling pathwayMap2k7 , Map3k1 , Mapk10 , Mapk8 , Mapk9
Fc epsilon receptor mediated signaling pathwayMap2k4 , Map2k7 , Mapk10 , Mapk8 , Mapk9 , Rac1
Fc gamma receptor mediated signaling pathwayCdc42 , Rac1
fibroblast growth factor signaling pathwaySpp1
glypican signaling pathwayMapk8 , Mapk9
gonadotropin-releasing hormone signaling pathwayCdc42 , Map2k4 , Map2k7 , Map3k1 , Map3k2 , Map3k3 , Map3k4 , Mapk10 , Mapk8 , Mapk9
hepatitis C virus infection pathwayMapk10 , Mapk8 , Mapk9 , Traf2
inflammatory response pathwayMapk8
influenza A virus infection pathwayMap2k4 , Map2k7 , Mapk10 , Mapk8 , Mapk9
insulin responsive facilitative sugar transporter mediated glucose transport pathwayRac1 , Rapgef1
insulin secretion pathwayCdc42
insulin signaling pathwayMapk10 , Mapk8 , Mapk9 , Rapgef1
interleukin-1 signaling pathwayMap3k3 , Map3k7 , Mapk8
interleukin-2 signaling pathwayMapk8 , Mapk9
interleukin-6 signaling pathwayMap2k4 , Rac1
kidney disease pathwaySpp1
Leishmania infection pathwayMap3k7
measles infection pathwayMap3k7
mercaptopurine pharmacodynamics pathwayRac1
mercaptopurine pharmacokinetics pathwayRac1
mitogen activated protein kinase signaling pathwayCdc42 , Dusp1 , Dusp10 , Dusp16 , Dusp8 , Map2k4 , Map2k7 , Map3k1 , Map3k11 , Map3k12 , Map3k2 , Map3k3 , Map3k4 , Map3k7 , Mapk10 , Mapk8 , Mapk8ip1 , Mapk8ip2 , Mapk8ip3 , Mapk9 , Rac1 , Traf2
mTOR signaling pathwayRac1
Mycobacterium tuberculosis infection pathwayMapk10 , Mapk8 , Mapk9
myocarditis pathwayRac1
N-cadherin signaling pathwayCdc42 , Mapk8 , Rac1
neurotrophic factor signaling pathwayCdc42 , Map2k7 , Map3k1 , Map3k3 , Mapk10 , Mapk8 , Mapk9 , Rac1 , Rapgef1
NOD-like receptor signaling pathwayMap3k7 , Mapk10 , Mapk8 , Mapk9
nuclear factor kappa B signaling pathwayMap3k7
p38 MAPK signaling pathwayCdc42 , Dusp1 , Dusp10 , Dusp16 , Map3k1 , Map3k10 , Map3k11 , Map3k3 , Map3k4 , Map3k7 , Mapk8ip2 , Rac1 , Traf2
p53 signaling pathwayMapk8 , Mapk9
pancreatic cancer pathwayCdc42 , Mapk10 , Mapk8 , Mapk9 , Rac1
phagocytosis pathwayRac1
phosphatidylinositol 3-kinase class I signaling pathwayRac1
platelet-derived growth factor signaling pathwayMap2k4 , Map2k7 , Mapk10 , Mapk8 , Mapk9 , Rac1
Reelin signaling pathwayMap2k7 , Map3k11 , Mapk8
renal cell cancer pathwayCdc42 , Rac1 , Rapgef1
Retinoic acid-inducible gene (RIG) I-like receptor signaling pathwayMap3k1 , Map3k7 , Mapk10 , Mapk8 , Mapk9 , Traf2
Rho/Rac/Cdc42 mediated signaling pathwayCdc42 , Map2k4 , Mapk8 , Rac1 , Rapgef1
small cell lung cancer pathwayTraf2
sphingosine 1-phosphate signaling pathwayCdc42 , Mapk8 , Rac1
syndecan signaling pathwayMapk8 , Rac1
T cell receptor signaling pathwayCdc42 , Map2k7 , Map3k7 , Mapk9
the extracellular signal-regulated Raf/Mek/Erk signaling pathwayMap3k1 , Map3k2 , Spp1
tioguanine pharmacodynamics pathwayRac1
Toll-like receptor signaling pathwayMap2k4 , Map2k7 , Map3k7 , Mapk10 , Mapk8 , Mapk9 , Rac1 , Spp1
Toxoplasma gondii infection pathwayMap3k7 , Mapk10 , Mapk8 , Mapk9
Trail mediated signaling pathwayMap2k4 , Map3k1 , Mapk8 , Traf2
transforming growth factor-beta Smad dependent signaling pathwayMap3k7
Trypanosoma cruzi infection pathwayMap2k4 , Mapk10 , Mapk8 , Mapk9
tumor necrosis factor mediated signaling pathwayMap2k7 , Map3k1 , Map3k3 , Map3k7 , Traf2
type 2 diabetes mellitus pathwayMapk10 , Mapk8 , Mapk9
type II interferon signaling pathwayMap3k1 , Map3k11
ubiquitin/proteasome degradation pathwayMap3k1
vascular endothelial growth factor signaling pathwayCdc42 , Rac1
Wnt signaling pathwayMap3k7 , Mapk10 , Mapk8 , Mapk9 , Rac1
Wnt signaling, non-canonical pathwayCdc42 , Map3k7 , Mapk10 , Mapk8 , Mapk9 , Rac1
Wnt signaling, the planar cell polarity pathwayRac1

References Associated with the c-Jun N-terminal kinases MAPK signaling pathway:

Ontology Path Diagram:

paths to the root

Import into Pathway Studio: