MAPK9 (mitogen-activated protein kinase 9)

2003-01-01   Fei Chen 

Health Effects Laboratory Division, NIOSH, 1095 Willowdale Rd, Morgantown, WV 26505, USA





The JNK2 gene maps on chromosome 5q35 spanning 58494bp. It contains 17 confirmed introns, 14 of which are alternative.


By alternative splicing, JNK2 gene encodes 12 types of transcripts that translate to 12 distinct JNK2 isoforms. The molecular weight of JNK2 is about 55 kD.



All JNK proteins contain a protein kinase domain that belong to a very extensive family of eukaryotic serine/threonine proteins kinase. A number of conserved regions have been identified in the catalytic domain of JNKs. In the N-terminal extremity of the catalytic domain there is a glycine-rich motif in the vicinity of a lysine residue, which has been shown to be involved in ATP binding. A conserved aspartic acid reside that is critical for the catalytic activity of kinase has also been identified in the central part of the catalytic domain.


JNK1 is ubiquitously expressed.


Cytoplasmic and nuclear


The members of JNK family act as an integration point for multiple intracellular biochemical signals governing a wide variety of cellular processes such as proliferation, differentiation, apoptosis, migration, transcriptional regulation, and development. JNK targets specific transcription factors and thus mediates immediate-early gene expression in response to various stress signals including ultraviolet (UV) radiation, oxidative stress, protein malfolding in endoplasmic reticulum, osmotical shock, and inflammatory mediators. These transcription factors include AP-1, ATF-2, Elk-1, p53, etc... Several upstream dual specific protein kinases, such as MKK4/SEK1 and MKK7, can activate JNK through phosphorylation of the conversed Thr-Pro-Tyr motif on JNK proteins. In mammalian cells, activated JNK can phosphorylate the N-terminus of c-Jun, which contains both JNK docking site and JNK phosphorylation site (ser63 and ser73), orJunD, which lacks a JNK docking site but contains a JNK phosphorylation site. JNK is unable to phosphorylate JunB due to the lack of a JNK phosphorylation site inJunB, despite there is a functional JNK docking site. Comparison of the binding activity of JNK isoforms demonstrates that JNK2 bind c-Jun approximately 25 times more efficiently than did JNK1. Therefore, individual members of the JNK family may selectively target specific transcription factors in vivo. One of the most important functions of JNK is the regulation of apoptosis. Emerging evidence indicates that JNK activation is obligatory for apoptosis induced by both receptor-mediated "extrinsic" pathway or mitochondria-mediated "intrinsic" pathway. JNK activation may contribute to the initiation of Fas-induced apoptosis, possibly through the amplification of autocrine or paracrine Fas signaling by JNK-dependent Fas ligand (FasL) gene expression. In addition, JNK has been indicated in the apoptosis induced by Daxx, a Fas death domain (FADD) interaction protein. Through its serine/threonine kinase activity, JNK may contribute to mitochondria-mediated apoptosis by phosphorylating pro- or anti-apoptoticBcl-2 family proteins. Finally, JNK has also been indicated as an important kinase phosphorylating p53 and subsequently facilitating p53-dependent apoptotic responses. Sustained JNK activation may be responsible for the enhanced apoptosis observed in RelA-/- or Ikkb-/- mouse embryonic fibroblasts treated with TNFa. It was suggested that deficiency of RelA or IKKb caused a decreased expression of XIAP or GADD45b, which may antagonize the activation of JNK activation. However, such speculation contradicts the previous observations indicating that both GADD45b and XIAP are activators, rather than inhibitors for JNK activation. Moreover, gene profiling in our recent studies indicated no substantial difference of basal or inducible GADD45b and XIAP mRNA in wild type cells and Ikkb-/- cells.

Implicated in

Entity name
Obesity, insulin resistance, neurodegenerative diseases, inflammation, cancer.


Pubmed IDLast YearTitleAuthors
110578972000Signal transduction by the JNK group of MAP kinases.Davis RJ et al
117135302001Induction of gadd45beta by NF-kappaB downregulates pro-apoptotic JNK signalling.De Smaele E et al
97106251998Stress-induced Fas ligand expression in T cells is mediated through a MEK kinase 1-regulated response element in the Fas ligand promoter.Faris M et al
97322641998JNK targets p53 ubiquitination and degradation in nonstressed cells.Fuchs SY et al
99256411999Multiple docking sites on substrate proteins form a modular system that mediates recognition by ERK MAP kinase.Jacobs D et al
80018191994JNK2 contains a specificity-determining region responsible for efficient c-Jun binding and phosphorylation.Kallunki T et al
114472972001Ubiquitin-protein ligase activity of X-linked inhibitor of apoptosis protein promotes proteasomal degradation of caspase-3 and enhances its anti-apoptotic effect in Fas-induced cell death.Suzuki Y et al
98278041998A family of stress-inducible GADD45-like proteins mediate activation of the stress-responsive MTK1/MEKK4 MAPKKK.Takekawa M et al
117135312001Inhibition of JNK activation through NF-kappaB target genes.Tang G et al
92156291997Daxx, a novel Fas-binding protein that activates JNK and apoptosis.Yang X et al

Other Information

Locus ID:

NCBI: 5601
MIM: 602896
HGNC: 6886
Ensembl: ENSG00000050748


dbSNP: 5601
ClinVar: 5601
TCGA: ENSG00000050748


Gene IDTranscript IDUniprot

Expression (GTEx)



PathwaySourceExternal ID
MAPK signaling pathwayKEGGko04010
ErbB signaling pathwayKEGGko04012
Autophagy - animalKEGGko04140
Wnt signaling pathwayKEGGko04310
Focal adhesionKEGGko04510
Tight junctionKEGGko04530
Toll-like receptor signaling pathwayKEGGko04620
T cell receptor signaling pathwayKEGGko04660
Fc epsilon RI signaling pathwayKEGGko04664
Insulin signaling pathwayKEGGko04910
GnRH signaling pathwayKEGGko04912
Progesterone-mediated oocyte maturationKEGGko04914
Adipocytokine signaling pathwayKEGGko04920
Type II diabetes mellitusKEGGko04930
Epithelial cell signaling in Helicobacter pylori infectionKEGGko05120
Colorectal cancerKEGGko05210
Pancreatic cancerKEGGko05212
MAPK signaling pathwayKEGGhsa04010
ErbB signaling pathwayKEGGhsa04012
Autophagy - animalKEGGhsa04140
Wnt signaling pathwayKEGGhsa04310
Focal adhesionKEGGhsa04510
Tight junctionKEGGhsa04530
Toll-like receptor signaling pathwayKEGGhsa04620
T cell receptor signaling pathwayKEGGhsa04660
Fc epsilon RI signaling pathwayKEGGhsa04664
Insulin signaling pathwayKEGGhsa04910
GnRH signaling pathwayKEGGhsa04912
Adipocytokine signaling pathwayKEGGhsa04920
Type II diabetes mellitusKEGGhsa04930
Epithelial cell signaling in Helicobacter pylori infectionKEGGhsa05120
Pathways in cancerKEGGhsa05200
Colorectal cancerKEGGhsa05210
Pancreatic cancerKEGGhsa05212
Neurotrophin signaling pathwayKEGGko04722
Neurotrophin signaling pathwayKEGGhsa04722
RIG-I-like receptor signaling pathwayKEGGko04622
RIG-I-like receptor signaling pathwayKEGGhsa04622
Progesterone-mediated oocyte maturationKEGGhsa04914
NOD-like receptor signaling pathwayKEGGko04621
NOD-like receptor signaling pathwayKEGGhsa04621
Chagas disease (American trypanosomiasis)KEGGko05142
Chagas disease (American trypanosomiasis)KEGGhsa05142
Protein processing in endoplasmic reticulumKEGGko04141
Protein processing in endoplasmic reticulumKEGGhsa04141
Hepatitis CKEGGko05160
Hepatitis CKEGGhsa05160
Osteoclast differentiationKEGGko04380
Osteoclast differentiationKEGGhsa04380
Influenza AKEGGko05164
Influenza AKEGGhsa05164
Salmonella infectionKEGGko05132
Salmonella infectionKEGGhsa05132
Herpes simplex infectionKEGGko05168
Herpes simplex infectionKEGGhsa05168
Dopaminergic synapseKEGGko04728
Dopaminergic synapseKEGGhsa04728
Retrograde endocannabinoid signalingKEGGhsa04723
Retrograde endocannabinoid signalingKEGGko04723
Epstein-Barr virus infectionKEGGhsa05169
Epstein-Barr virus infectionKEGGko05169
Hepatitis BKEGGhsa05161
TNF signaling pathwayKEGGhsa04668
TNF signaling pathwayKEGGko04668
Prolactin signaling pathwayKEGGhsa04917
Prolactin signaling pathwayKEGGko04917
Non-alcoholic fatty liver disease (NAFLD)KEGGhsa04932
Non-alcoholic fatty liver disease (NAFLD)KEGGko04932
Ras signaling pathwayKEGGhsa04014
FoxO signaling pathwayKEGGhsa04068
Inflammatory mediator regulation of TRP channelsKEGGhsa04750
Inflammatory mediator regulation of TRP channelsKEGGko04750
cAMP signaling pathwayKEGGhsa04024
cAMP signaling pathwayKEGGko04024
Choline metabolism in cancerKEGGhsa05231
Choline metabolism in cancerKEGGko05231
MAPK (JNK) signalingKEGGhsa_M00688
MAPK (JNK) signalingKEGGM00688
Sphingolipid signaling pathwayKEGGhsa04071
Sphingolipid signaling pathwayKEGGko04071
Immune SystemREACTOMER-HSA-168256
Innate Immune SystemREACTOMER-HSA-168249
Toll-Like Receptors CascadesREACTOMER-HSA-168898
Toll Like Receptor 10 (TLR10) CascadeREACTOMER-HSA-168142
MyD88 cascade initiated on plasma membraneREACTOMER-HSA-975871
MAP kinase activation in TLR cascadeREACTOMER-HSA-450294
JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1REACTOMER-HSA-450321
MAPK targets/ Nuclear events mediated by MAP kinasesREACTOMER-HSA-450282
Activation of the AP-1 family of transcription factorsREACTOMER-HSA-450341
Toll Like Receptor 3 (TLR3) CascadeREACTOMER-HSA-168164
MyD88-independent TLR3/TLR4 cascadeREACTOMER-HSA-166166
TRIF-mediated TLR3/TLR4 signalingREACTOMER-HSA-937061
Toll Like Receptor 5 (TLR5) CascadeREACTOMER-HSA-168176
Toll Like Receptor 7/8 (TLR7/8) CascadeREACTOMER-HSA-168181
MyD88 dependent cascade initiated on endosomeREACTOMER-HSA-975155
TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activationREACTOMER-HSA-975138
Toll Like Receptor 9 (TLR9) CascadeREACTOMER-HSA-168138
Toll Like Receptor 4 (TLR4) CascadeREACTOMER-HSA-166016
Activated TLR4 signallingREACTOMER-HSA-166054
MyD88:Mal cascade initiated on plasma membraneREACTOMER-HSA-166058
Toll Like Receptor 2 (TLR2) CascadeREACTOMER-HSA-181438
Toll Like Receptor TLR1:TLR2 CascadeREACTOMER-HSA-168179
Toll Like Receptor TLR6:TLR2 CascadeREACTOMER-HSA-168188
Fc epsilon receptor (FCERI) signalingREACTOMER-HSA-2454202
FCERI mediated MAPK activationREACTOMER-HSA-2871796
Cellular responses to stressREACTOMER-HSA-2262752
Cellular SenescenceREACTOMER-HSA-2559583
Oxidative Stress Induced SenescenceREACTOMER-HSA-2559580
Insulin resistanceKEGGhsa04931
AGE-RAGE signaling pathway in diabetic complicationsKEGGko04933
AGE-RAGE signaling pathway in diabetic complicationsKEGGhsa04933
Apoptosis - multiple speciesKEGGko04215
Apoptosis - multiple speciesKEGGhsa04215
Endocrine resistanceKEGGko01522
Endocrine resistanceKEGGhsa01522
Th1 and Th2 cell differentiationKEGGko04658
Th1 and Th2 cell differentiationKEGGhsa04658
Th17 cell differentiationKEGGko04659
Th17 cell differentiationKEGGhsa04659
IL-17 signaling pathwayKEGGko04657
Fluid shear stress and atherosclerosisKEGGko05418
IL-17 signaling pathwayKEGGhsa04657
Fluid shear stress and atherosclerosisKEGGhsa05418
Mitophagy - animalKEGGko04137
Mitophagy - animalKEGGhsa04137

Protein levels (Protein atlas)

Not detected


Entity IDNameTypeEvidenceAssociationPKPDPMIDs


Pubmed IDYearTitleCitations
203796142010Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.62
147245882004Inhibition of JNK reduces G2/M transit independent of p53, leading to endoreduplication, decreased proliferation, and apoptosis in breast cancer cells.58
188388642008JNK2-dependent regulation of SIRT1 protein stability.57
213646372010JNK phosphorylates Yes-associated protein (YAP) to regulate apoptosis.49
125384932003C-Jun NH(2)-terminal kinase mediates proliferation and tumor growth of human prostate carcinoma.43
221057592012Elevated hepatic multidrug resistance-associated protein 3/ATP-binding cassette subfamily C 3 expression in human obstructive cholestasis is mediated through tumor necrosis factor alpha and c-Jun NH2-terminal kinase/stress-activated protein kinase-signaling pathway.33
191547852009Ultrafine particles from diesel engines induce vascular oxidative stress via JNK activation.30
231718492012JNK2 is activated during ER stress and promotes cell survival.30
170748092007TBP is differentially regulated by c-Jun N-terminal kinase 1 (JNK1) and JNK2 through Elk-1, controlling c-Jun expression and cell proliferation.29
155274952004Interaction of Neisseria meningitidis with human brain microvascular endothelial cells: role of MAP- and tyrosine kinases in invasion and inflammatory cytokine release.28


Fei Chen

MAPK9 (mitogen-activated protein kinase 9)

Atlas Genet Cytogenet Oncol Haematol. 2003-01-01

Online version: