Mitogen-activated protein kinase 8 (JNK1) and Mitogen-activated protein kinase 9 (JNK2) (JNK1/JNK2)

Mitogen-activated protein kinase 8 (JNK1) and Mitogen-activated protein kinase 9 (JNK2) are closely related serine/threonine kinases belonging to the c-Jun N-terminal kinase family, which is a subfamily of the mitogen-activated protein kinases (MAPKs). These kinases are activated in response to cellular stress signals, cytokines, and growth factors. Upon activation, JNK1 and JNK2 phosphorylate various nuclear and cytoplasmic substrates, including the transcription factor c-Jun, leading to regulation of genes involved in cell proliferation, differentiation, apoptosis, autophagy, and immune responses. JNK1/2 are ubiquitously expressed and have overlapping, but not completely redundant, roles in tissue homeostasis. Dysregulation of JNK1/2 activity is implicated in the pathogenesis of several diseases, including cancer, inflammatory disorders, and neurodegeneration, making them important therapeutic targets. The development of selective inhibitors remains a key challenge due to the highly conserved nature of their ATP-binding sites.

Other names

c-Jun N-terminal kinase 1c-Jun N-terminal kinase 2JNK1 (MAPK8)JNK2 (MAPK9)Stress-activated protein kinase (SAPK)PRKM8 (JNK1)PRKM9 (JNK2)

ATP-competitive inhibition (occupying the kinase ATP-binding pocket, many with poor isoform selectivity); Allosteric inhibition (e.g. interfering with JNK–JIP scaffold interactions); Inhibitors lead to downregulation of JNK-mediated phosphorylation of target proteins such as c-Jun, thereby reducing transcriptional activity of stress response genes.