JNK2/SAPK1 Human
Description
Molecular Structure and Isoforms
JNK2 is encoded by the jnk2 gene and exists in multiple isoforms generated through alternative splicing. Key features include:
JNK2 shares structural homology with JNK1 and JNK3 but exhibits distinct substrate preferences and tissue expression patterns. For example, JNK2 is more critical for JNK1 dephosphorylation in macrophages , while JNK3 is primarily neural-specific .
Regulatory Mechanisms
JNK2 activity is tightly controlled by upstream kinases (e.g., MKK4/7) and phosphatases:
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Activation: Triggered by stress signals like ER stress, UV radiation, or cytokines .
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Inactivation: Dual-specificity phosphatases (DUSPs) such as MKP1 and MKP5 modulate JNK2 phosphorylation. MKP5 preferentially dephosphorylates JNK1, whereas MKP1 targets p38α .
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Cross-regulation: JNK2 antagonizes JNK1 in myeloid leukemia cells, suppressing differentiation signals .
Biological Functions
JNK2/SAPK1 regulates diverse cellular processes:
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Cell Survival: During ER stress, JNK2 prevents lysosomal acidification, sustaining autophagic flux and survival .
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Immune Modulation: In CD8+ T cells, JNK2 inhibits IL-2 production and proliferation, contrasting with JNK1’s pro-activation role .
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Transcriptional Control: Phosphorylates c-Jun, ATF2, and Sp1, enhancing their stability and nuclear localization .
Disease Associations
Dysregulated JNK2 signaling is implicated in multiple pathologies:
Research Tools and Applications
Recombinant JNK2/SAPK1 (e.g., Human Recombinant SAPK1/JNK2) is widely used to study kinase activity:
| Parameter | Specification |
|---|---|
| Source | Escherichia coli |
| Purity | >95% by SDS-PAGE |
| Activity | >300 U/mg (1 U = 1 pmol/min phosphate transfer to c-Jun) |
| Storage | 50% glycerol, -20°C; avoid freeze-thaw cycles |
Key Research Findings
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Cancer: JNK2 activation in squamous cell carcinoma correlates with reduced p16 expression and enhanced Ras-driven transformation .
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ER Stress: JNK2 silencing exacerbates CHOP expression and BiP depletion, sensitizing cells to apoptosis .
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Immune Regulation: JNK2-deficient CD8+ T cells hyperproliferate due to unregulated IL-2 production .
Contradictory Roles in Apoptosis
JNK2 exhibits context-dependent functions:
Product Specs
Product Science Overview
JNK2, also known as c-Jun N-terminal kinase 2, is a member of the stress-activated protein kinase (SAPK) family. It is encoded by the MAPK9 gene in humans and plays a crucial role in various cellular processes, including proliferation, differentiation, and apoptosis. JNK2 is part of the larger mitogen-activated protein kinase (MAPK) pathway, which is involved in transmitting extracellular signals to the cell nucleus.
JNK2 is a serine/threonine kinase that is activated by dual phosphorylation on threonine and tyrosine residues. This activation is typically mediated by upstream kinases such as MKK4 (SEK1) and MKK7. Upon activation, JNK2 translocates to the nucleus, where it phosphorylates various transcription factors, including c-Jun, ATF-2, and Elk-1 .
JNK2 is involved in several physiological processes:
- Cell Proliferation and Differentiation: JNK2 regulates the expression of genes involved in cell cycle progression and differentiation.
- Apoptosis: JNK2 activation can lead to apoptosis in response to various stress signals, including UV radiation and oxidative stress .
- Immune Response: JNK2 plays a role in the immune response by regulating the production of cytokines and other immune mediators .
Recombinant JNK2 is produced using recombinant DNA technology, where the human MAPK9 gene is cloned into an expression vector and introduced into a host cell, such as E. coli or mammalian cells. The expressed protein is then purified for use in research and therapeutic applications. Recombinant JNK2 is commonly used in studies to understand its role in cellular signaling and to develop potential therapeutic interventions for diseases where JNK2 is implicated .
Research on JNK2 has provided insights into its role in various diseases, including cancer, neurodegenerative disorders, and inflammatory diseases. Inhibitors targeting JNK2 are being explored as potential therapeutic agents for these conditions. For example, JNK2 inhibitors have shown promise in reducing tumor growth and improving outcomes in preclinical models of cancer .
