Mitogen-activated protein kinase 8 (JNK1), Mitogen-activated protein kinase 9 (JNK2), and Mitogen-activated protein kinase 10 (JNK3) (JNK1, JNK2, JNK3)

Mitogen‐activated protein kinases known as c-Jun N-terminal kinases (JNKs) are a subfamily within the larger MAPK family. There are three main isoforms encoded by separate genes—mitogen‐activated protein kinase 8 (MAPK8/JNK1), mitogen‐activated protein kinase 9 (MAPK9/JNK2), and mitogen‐activated protein kinase 10 (MAPK10/JNK3)—with overlapping but distinct tissue distributions. These enzymes are evolutionarily conserved serine/threonine kinases that play central roles in cellular signal transduction pathways activated by stress stimuli such as cytokines, UV irradiation, oxidative stress, and growth factors. Upon activation by upstream kinases MKK4/MKK7 through dual phosphorylation on threonine and tyrosine residues, they phosphorylate transcription factors like c-Jun to regulate gene expression related to apoptosis, inflammation response, cell proliferation/differentiation/death processes, embryonic development, immune defense mechanisms, autophagy regulation, and neuronal functions. Dysregulation or overactivation of the JNK pathway is implicated in various diseases including cancer progression/metastasis, chronic inflammatory conditions, neurodegenerative disorders such as Parkinson’s disease, cardiovascular diseases and metabolic syndromes. Pharmacological inhibition of these kinases is an area of active therapeutic research; however safety concerns remain due to their fundamental roles across many physiological processes.

Other names

c-Jun N-terminal kinasec-jun NH2-terminal kinaseStress-activated protein kinase (SAPK)SAPK gammaMAP kinase 8/9/10

Inhibition of serine/threonine phosphorylation activity of JNKs to block downstream signaling pathways involved in apoptosis, inflammation, or cell proliferation.