c-Jun N-terminal kinase (JNK) (JNK (also known as SAPK, Stress-activated protein kinase))

c-Jun N-terminal kinases (JNKs) are a subfamily of mitogen-activated protein kinases (MAPKs) involved in cellular responses to stress and pro-inflammatory signals[3][9]. The JNK family consists of three main enzymes—JNK1 (MAPK8), JNK2 (MAPK9), and JNK3 (MAPK10)—which phosphorylate the transcription factor c-Jun and regulate the activity of other transcription factors (such as ATF2, ELK1, SMAD4, p53, HSF1)[9][3]. JNK1 and JNK2 are widely expressed in most tissues, while JNK3 is primarily found in the brain, heart, and testis[1][2][3][9]. JNK activation leads to regulation of apoptosis, proliferation, differentiation, immune and stress responses, and is implicated in diseases such as cancer, inflammation, neurodegeneration, and metabolic disorders[4][2][8]. Pharmacological inhibition of JNKs is pursued for therapeutic intervention in several disease indications, but challenges remain due to the pathway’s broad physiological roles and isoform-specific functions[4][2].

Other names

JNKStress-activated protein kinase (SAPK)JNK1 (MAPK8)JNK2 (MAPK9)JNK3 (MAPK10)c-Jun kinaseMAPK8/9/10

Inhibition of kinase activity through blocking ATP-binding site; Inhibition by substrate-competitive mechanisms (e.g., via scaffold peptide D-JNKI1); Downregulation of JNK-mediated phosphorylation of c-Jun and other substrates