MAPK9 Human
Description
Introduction to MAPK9 Human
MAPK9 (Mitogen-Activated Protein Kinase 9) is a serine/threonine kinase encoded by the MAPK9 gene in humans. It belongs to the c-Jun N-terminal kinase (JNK) subfamily, which includes MAPK8 (JNK1) and MAPK9 (JNK2). MAPK9 acts as a critical regulator of cellular responses to stress, growth signals, and inflammatory stimuli, influencing processes such as apoptosis, proliferation, and transcriptional regulation .
Key Isoforms
MAPK9 exists in multiple isoforms due to alternative splicing, including JNK2α1, JNK2α2, JNK2β1, and JNK2β2, which differ in their C-terminal domains and regulatory interactions . These isoforms exhibit distinct subcellular localization and functional roles.
Signaling Pathways
MAPK9 is activated via the JNK cascade, where upstream kinases MAP2K4 (MKK4) and MAP2K7 (MKK7) phosphorylate its Thr183, Pro185, and Tyr185 residues . Activated MAPK9 phosphorylates transcription factors such as:
Cellular Processes
| Process | Mechanism | Clinical Relevance |
|---|---|---|
| Apoptosis | Phosphorylates pro-apoptotic factors (e.g., Bcl-2 family proteins) | Tumor suppression |
| EMT (Epithelial-Mesenchymal Transition) | Upregulates N-cadherin and vimentin, downregulates E-cadherin | Glioma progression |
| T-cell Differentiation | Required for Th1 cell polarization in response to TCR stimulation | Immune regulation |
Glioma Prognosis
A 2023 study on 150 glioma patients found:
| Parameter | Low MAPK9 | High MAPK9 | p-value |
|---|---|---|---|
| WHO Grade (GBM vs. LGG) | 8/96 | 43/54 | p<0.001 |
| IDH-Wildtype Status | 6/47 | 41/47 | p<0.001 |
| 3-Year Survival Rate | 30/119 | 1/31 | p<0.001 |
High MAPK9 expression correlates with aggressive glioma phenotypes (e.g., IDH-wildtype, non-codel) and poor survival outcomes .
Wnt/β-Catenin Signaling
MAPK9 promotes glioma progression by activating Wnt/β-catenin pathways, leading to:
Experimental Insights from Glioma Models
| Experiment | MAPK9 Overexpression | MAPK9 Knockdown |
|---|---|---|
| Proliferation (CCK-8) | ↑ 1.5–2x vs. control | ↓ 40–50% vs. control |
| Migration (Transwell) | ↑ 2–3x vs. control | ↓ 60–70% vs. control |
| EMT Markers | ↑ N-cadherin, vimentin; ↓ E-cadherin | ↓ N-cadherin, vimentin; ↑ E-cadherin |
These findings confirm MAPK9’s role in enhancing glioma cell migration and invasion .
Interaction Network
MAPK9 interacts with:
Recombinant MAPK9 Applications
Recombinant MAPK9 is used in:
JNK Cascade Activation
| Step | Component | Function |
|---|---|---|
| 1. Signal Initiation | TLRs, TNFα, UV | Activate upstream MAP3Ks (e.g., TAK1) |
| 2. MKK Activation | MAP2K4/MAP2K7 | Phosphorylate MAPK9 Thr/Pro/Tyr |
| 3. Target Phosphorylation | c-Jun, ATF2 | Regulate stress-response genes |
Product Specs
Product Science Overview
MAPK9 is involved in the integration of multiple biochemical signals. It targets specific transcription factors, mediating immediate-early gene expression in response to various cell stimuli . This kinase is closely related to MAPK8, and both are involved in UV radiation-induced apoptosis, which is thought to be related to the cytochrome c-mediated cell death pathway .
MAPK9 plays a significant role in:
- Proliferation and Differentiation: It helps in the regulation of cell growth and differentiation.
- Transcription Regulation: It influences the transcription of genes in response to cellular stimuli.
- Development: It is involved in the development of various tissues and organs.
- Apoptosis: It is crucial in the process of programmed cell death, particularly in response to stress signals like UV radiation .
The recombinant form of MAPK9 is typically produced using Escherichia coli (E. coli) expression systems. The gene encoding MAPK9 is cloned into an expression vector, which is then introduced into E. coli cells. The bacteria are cultured, and the protein is expressed and subsequently purified using various chromatographic techniques .
MAPK9 has been associated with several diseases, including multiple endocrine neoplasia and kidney disease . Its role in apoptosis and cell cycle regulation makes it a significant target for cancer research. Understanding the pathways and mechanisms involving MAPK9 can lead to the development of new therapeutic strategies for various diseases.
