MAPK8 (JNK1): A Key Stress-Activated Kinase in Inflammation, Apoptosis, and Cancer
Explore the genomic, functional, and clinical significance of MAPK8 (JNK1), including its role in disease, tissue expression, mutations, and therapeutic relevance.
Gene Information Card
| Symbol | MAPK8 |
|---|---|
| Full Name | Mitogen-Activated Protein Kinase 8 |
| Gene Type | Protein coding |
| Chromosomal Location | 10q11.22 (GRCh38) |
| NCBI Gene ID | 5599 ncbi.nlm.nih.gov/gene/5599 |
| Ensembl ID | ENSG00000107643 |
| UniProt ID | P45983 |
| OMIM ID | 601158 |
| HGNC ID | 6881 |
| Aliases | JNK1, JNK-1, PRKM8, SAPK1, JNK1A2, JNK21B1/2 |
Description
MAPK8 (Mitogen-Activated Protein Kinase 8) encodes the JNK1 protein, a serine/threonine kinase belonging to the MAP kinase family. JNK1 is activated by various stress stimuli (e.g., UV radiation, inflammatory cytokines, oxidative stress) and plays a central role in signaling cascades that regulate cell proliferation, differentiation, apoptosis, and inflammation. It is involved in the JNK signaling pathway, which is critical for cellular responses to environmental stress and has been implicated in numerous diseases, including cancer, neurodegenerative disorders, and inflammatory conditions.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hepatocellular carcinoma | JNK1 activation promotes cell survival and proliferation; overexpression or constitutive activation contributes to tumorigenesis. | COSMIC: MAPK8 mutations found in liver cancer; PubMed studies show JNK1 promotes HCC growth. |
| Type 2 diabetes | JNK1 activation in insulin-responsive tissues impairs insulin signaling via IRS-1 serine phosphorylation, leading to insulin resistance. | ClinVar: variants associated with metabolic traits; multiple studies link JNK1 to diabetes. |
| Inflammatory bowel disease (IBD) | JNK1 regulates pro-inflammatory cytokine production and intestinal epithelial cell apoptosis, contributing to mucosal inflammation. | ClinVar: gene expression changes; animal models show JNK1 deficiency reduces colitis. |
| Neurodegenerative disorders (e.g., Alzheimer's disease) | JNK1 phosphorylates tau protein and promotes amyloid-beta-induced neuronal apoptosis, contributing to neurodegeneration. | UniProt: JNK1 implicated in tau phosphorylation; PubMed evidence. |
| Rheumatoid arthritis | JNK1 mediates inflammatory cytokine signaling and synovial fibroblast activation, driving joint inflammation and destruction. | ClinVar: gene expression in synovium; JNK inhibitors reduce arthritis in models. |
| Cardiovascular diseases (e.g., cardiac hypertrophy) | JNK1 activation in cardiac myocytes promotes hypertrophic growth and apoptosis in response to stress. | PubMed: JNK1 knockout attenuates hypertrophy; ClinVar: variants linked to cardiac phenotypes. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 25.4 | High |
| Adrenal gland | 20.1 | High |
| Lymph node | 18.7 | High |
| Liver | 15.3 | Medium |
| Kidney | 12.8 | Medium |
| Heart | 10.2 | Medium |
| Lung | 8.5 | Low |
| Skeletal muscle | 6.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa (cervical cancer) | 22.3 | High expression; JNK1 active in stress response. |
| K562 (leukemia) | 18.9 | High; JNK1 involved in proliferation. |
| A549 (lung cancer) | 15.2 | Moderate; JNK1 regulates apoptosis. |
| HepG2 (liver cancer) | 14.7 | Moderate; JNK1 promotes tumor growth. |
| MCF7 (breast cancer) | 9.8 | Low; JNK1 expression variable. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.137C>T (p.Pro46Leu) | Missense | 0.5% (COSMIC) | Potential loss of function; affects kinase activity. |
| c.458A>G (p.Asn153Ser) | Missense | 0.2% (COSMIC) | Gain of function; increased JNK signaling. |
| c.1021G>A (p.Val341Met) | Missense | 0.1% (COSMIC) | Unknown; may alter substrate specificity. |
| c.1123C>T (p.Arg375Trp) | Missense | 0.3% (ClinVar) | Likely pathogenic; associated with neurodevelopmental delay. |
| c.1543A>G (p.Thr515Ala) | Missense | 0.05% (COSMIC) | Loss of function; reduced kinase activity. |
Mutation functional classification
Loss of Function (LOF)
Mutations that reduce or abolish JNK1 kinase activity, impairing stress signaling and apoptosis. Examples include p.Pro46Leu and p.Thr515Ala, which may lead to decreased phosphorylation of downstream targets.
Gain of Function (GOF)
Mutations that enhance JNK1 activity, promoting cell proliferation and survival. p.Asn153Ser is an example that increases kinase activity, potentially contributing to oncogenesis.
Dominant Negative (DN)
Certain mutations may produce a dominant-negative effect, where the mutant protein interferes with wild-type JNK1 function, disrupting JNK signaling. This is observed in some cancer-associated variants, though specific examples require further validation.
View complete mutation data：
Gene Ontology (GO)
| • Protein kinase activity | • ATP binding |
| • MAP kinase activity | • Signal transduction |
| • Apoptotic process | • Cellular response to stress |
| • JNK cascade | • Inflammatory response |
| • Regulation of transcription | • Protein phosphorylation |
Pathways
• JNK signaling pathway
• MAPK signaling pathway
• TNF signaling pathway
• Apoptosis
• IL-17 signaling pathway
• Toll-like receptor signaling pathway
• Neurotrophin signaling pathway
• Fc epsilon RI signaling pathway
Protein Summary
The MAPK8 gene encodes JNK1, a 384-amino acid protein (UniProt P45983) with a molecular weight of ~48 kDa. JNK1 contains a serine/threonine kinase domain and is activated by dual phosphorylation on Thr-183 and Tyr-185 by upstream kinases (MKK4/MKK7). Once activated, JNK1 translocates to the nucleus and phosphorylates transcription factors such as c-Jun, ATF-2, and p53, modulating gene expression. It also phosphorylates cytoplasmic substrates like Bcl-2 and IRS-1, influencing apoptosis and insulin signaling. JNK1 is ubiquitously expressed but shows high levels in brain, adrenal gland, and immune tissues. Its activity is tightly regulated by phosphatases and scaffold proteins. Dysregulation of JNK1 is linked to cancer, metabolic disorders, and inflammatory diseases, making it a potential therapeutic target.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| MAPK8 Knockout HEK293 Cell Line | EDJ-KQ193 | Human | 5599 | Details Get a Quote |
| MAPK8IP1 Knockout HEK293 Cell Line | EDJ-KQ702 | Human | 9479 | Details Get a Quote |
| MAPK8IP2 Knockout HEK293 Cell Line | EDJ-KQ703 | Human | 23542 | Details Get a Quote |
| MAPK8IP3 Knockout HEK293 Cell Line | EDJ-KQ704 | Human | 23162 | Details Get a Quote |
| MAPK8IP3 Knockout A-549 Cell Line | EDJ-KQ18153 | Human | 23162 | Details Get a Quote |
| MAPK8 Knockout A-549 Cell Line | EDJ-KQ19283 | Human | 5599 | Details Get a Quote |
| MAPK8 Knockout HCT 116 Cell Line | EDJ-KQ19285 | Human | 5599 | Details Get a Quote |
| MAPK8 Knockout HeLa Cell Line | EDJ-KQ19286 | Human | 5599 | Details Get a Quote |
| MAPK8IP1 Knockout A-549 Cell Line | EDJ-KQ19287 | Human | 9479 | Details Get a Quote |
| MAPK8IP1 Knockout HCT 116 Cell Line | EDJ-KQ19288 | Human | 9479 | Details Get a Quote |
| MAPK8IP1 Knockout HeLa Cell Line | EDJ-KQ19289 | Human | 9479 | Details Get a Quote |
| MAPK8IP2 Knockout A-549 Cell Line | EDJ-KQ19290 | Human | 23542 | Details Get a Quote |
| MAPK8IP2 Knockout HCT 116 Cell Line | EDJ-KQ19291 | Human | 23542 | Details Get a Quote |
| MAPK8IP3 Knockout HCT 116 Cell Line | EDJ-KQ19293 | Human | 23162 | Details Get a Quote |
| MAPK8IP3 Knockout HeLa Cell Line | EDJ-KQ19294 | Human | 23162 | Details Get a Quote |
Displaying Records 1 To 15 Of 16 Records
