C-Jun N-terminal kinase

C-Jun N-terminal kinase (JNK) is a type of mitogen-activated protein kinase (MAPK) that is involved in regulating various cellular processes, including cell proliferation, apoptosis, and inflammation. JNK is part of the larger MAPK family, which also includes extracellular signal-regulated kinases (ERKs) and p38 MAP kinases.

Structure and Isoforms

JNKs are encoded by three genes: MAPK8, MAPK9, and MAPK10, which correspond to JNK1, JNK2, and JNK3, respectively. These kinases are expressed in different tissues and have distinct roles in cellular signaling. JNK1 and JNK2 are ubiquitously expressed, while JNK3 is primarily found in the brain, heart, and testis.

Activation and Function

JNK is activated by a variety of stress signals, including cytokines, ultraviolet radiation, heat shock, and osmotic stress. Upon activation, JNK translocates to the nucleus where it phosphorylates and activates transcription factors such as c-Jun, a component of the activator protein 1 (AP-1) complex. This leads to changes in gene expression that mediate cellular responses to stress.

JNK plays a critical role in:

• Apoptosis: JNK can promote apoptosis by activating pro-apoptotic genes and inhibiting anti-apoptotic signals.
• Cell proliferation: JNK influences cell cycle progression and can either promote or inhibit proliferation depending on the context.
• Inflammation: JNK is involved in the regulation of inflammatory cytokines and can modulate immune responses.

Pathological Implications

Dysregulation of JNK signaling has been implicated in various diseases, including:

• Cancer: Aberrant JNK activity can contribute to tumorigenesis by affecting cell proliferation and apoptosis.
• Neurodegenerative diseases: JNK is involved in neuronal apoptosis and has been linked to conditions such as Alzheimer's disease and Parkinson's disease.
• Diabetes: JNK signaling is associated with insulin resistance and the development of type 2 diabetes.

Therapeutic Targeting

Given its role in disease, JNK is a potential target for therapeutic intervention. Inhibitors of JNK are being explored for their potential to treat inflammatory diseases, cancer, and neurodegenerative disorders.

Also see

• Mitogen-activated protein kinase
• Apoptosis
• Signal transduction
• Transcription factor