Mitogen-activated protein kinase 9 (JNK2) (JNK2)

Mitogen-activated protein kinase 9 (MAPK9), commonly known as JNK2, is a member of the c-Jun N-terminal kinase family within the mitogen-activated protein kinase (MAPK) superfamily [4, 13, 14]. It is a stress-activated serine/threonine-protein kinase that responds to various extracellular stimuli, including proinflammatory cytokines, UV radiation, and oxidative stress [1, 2, 4, 12]. Upon activation by upstream kinases MKK4 and MKK7, JNK2 phosphorylates a variety of transcription factors, most notably c-Jun and ATF2, thereby regulating gene expression programs involved in cell proliferation, differentiation, and apoptosis [4, 13, 14, 16]. In disease contexts, JNK2 is frequently dysregulated; it promotes tumorigenesis in cancers such as melanoma and squamous cell carcinoma, and plays a critical role in the pathogenesis of inflammatory and metabolic disorders like type 2 diabetes and obesity [1, 2, 5, 9, 19]. Therapeutic targeting of JNK2 primarily involves small-molecule inhibitors that compete for the ATP-binding site or covalently modify the kinase [6, 7, 9, 12, 15]. However, drug development faces significant challenges, including the need for isoform selectivity to avoid off-target effects and the dual role of JNK signaling, which can act as either a tumor promoter or a tumor suppressor depending on the cellular context [6, 7, 9, 20].

Other names

c-Jun N-terminal kinase 2Stress-activated protein kinase 1aSAPK1aJNK-55PRKM9SAPK-alphaJun kinaseMAP kinase 9

ATP-competitive inhibition, Covalent inhibition, Allosteric modulation, Substrate-competitive inhibition