MAPK10

MAPK10 Background

The MAPK10 gene encodes the mitogen-activated protein kinase 10, an enzyme also known as c-Jun N-terminal kinase 3 (JNK3) ^[1][2]. JNK3 expression is largely restricted to the brain, heart, and testis ^[3]. As a serine/threonine-protein kinase, MAPK10/JNK3 is involved in various processes such as neuronal proliferation, differentiation, migration, and programmed cell death. Extracellular stimuli such as proinflammatory cytokines or physical stress stimulate the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. In this cascade, two dual specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and activate MAPK10/JNK3. In turn, MAPK10/JNK3 phosphorylates many transcription factors, primarily components of AP-1 such as JUN and ATF2 and thus regulates AP-1 transcriptional activity, eventually inducing cell proliferation, differentiation and stress responses ^[2][4-6]. Targeted deletion of JNK3 not only reduces the stress-induced JNK activity but also protects mice from a brain injury after cerebral ischemia–hypoxia ^[7]. The downstream mechanism of JNK3-mediated apoptosis may include the induction of Bim and Fas and the mitochondrial release of cytochrome c ^[7]. These results suggest that JNK3 is a potential target for neuroprotection therapies in stroke ^[7].

[1] Yoshida S, Harada H, et al. Head-to-head juxtaposition of Fas-associated phosphatase-1 (FAP-1) and c-Jun NH2-terminal kinase 3 (JNK3) genes: genomic structure and seven polymorphisms of the FAP-1 gene [J]. J. Hum. Genet. 2002, 47 (11): 614-9.
[2] Gupta S, Barrett T, et al. Selective interaction of JNK protein kinase isoforms with transcription factors [J]. EMBO J. 1996, 15 (11): 2760-70.
[3] Davis RJ. Signal transduction by the JNK group of MAP kinases.
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[4] Dérijard B, Hibi M, et al. JNK1: a protein kinase stimulated by UV light and Ha-Ras that binds and phosphorylates the c-Jun activation domain. Cell 1994, 76: 1025-1037.
[5] Kyriakis J, Banerjee P, The stress-activated protein kinase subfamily of c-Jun kinases. Nature 1994, 369: 156-160.
[6] Nishina H, Wada T, et al. Physiological roles of SAPK/JNK signaling pathway. J Biochem. 2004 Aug;136(2):123-6.
[7] Chia-Yi Kuan, Alan J. Whitmarsh, et al. A critical role of neural-specific JNK3 for ischemic apoptosis [J]. Proc Natl Acad Sci U S A. 2003 Dec 9; 100(25): 15184-15189.