c-Jun N-terminal kinase (JNK)

The **c-Jun N-terminal kinase (JNK)** is a member of the mitogen-activated protein kinase (MAPK) family of enzymes, originally identified by its ability to phosphorylate the c-Jun transcription factor on Ser-63 and Ser-73[1][5]. It is activated in response to a wide range of cellular stresses and extracellular stimuli, such as cytokines, UV irradiation, heat shock, and osmotic stress[1][4][5]. JNK signaling is crucial in regulating numerous cellular processes, including apoptosis, proliferation, differentiation, immune response, and gene expression[1][3][5][6]. There are three genes encoding JNK proteins: JNK1 and JNK2, which are widely expressed, and JNK3, which is mainly restricted to the brain, heart, and testis[1][5][9]. Dysregulation of JNK signaling is implicated in several diseases, notably cancer (by influencing tumor growth, metastatic potential, and cancer stem cell populations), neurodegenerative disorders (such as Alzheimer's disease), chronic inflammation, diabetes, and liver disease[2][4][5][9]. JNK is activated by dual phosphorylation within its activation loop (Thr-Pro-Tyr motif) by the upstream kinases MKK4 and MKK7[1][3]. Therapeutic targeting includes ATP-competitive, non-kinase, and substrate-competitive inhibition, but clinical development is challenged by JNK’s roles in maintaining cellular homeostasis and its context-dependent tumor-suppressive functions[2][4].

Other names

c-Jun N-terminal kinasesJNKstress-activated protein kinaseSAPK

ATP-competitive inhibition of JNK activity; Non-kinase inhibition; Substrate-competitive inhibition