c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38 MAPK) (JNK and p38 MAPK)

The c-Jun N-terminal kinases (JNK) and p38 mitogen-activated protein kinases (MAPK) are two distinct subfamilies of the mitogen-activated protein kinase (MAPK) superfamily, collectively referred to as stress-activated protein kinases (SAPKs) (Kyriakis & Avruch, 2012). These enzymes are critical mediators of cellular responses to environmental stressors, such as ultraviolet radiation, oxidative stress, and pro-inflammatory cytokines like tumor necrosis factor-alpha (TNF-α) (Zarubin & Han, 2005). JNK signaling primarily regulates apoptosis, cell growth, and differentiation by phosphorylating transcription factors such as c-Jun and ATF2 (Bubici & Papa, 2014). The p38 MAPK pathway is a central regulator of the inflammatory response, controlling the production of cytokines and the activation of various immune cells (Arthur & Ley, 2013). Dysregulation of these pathways is strongly linked to the pathogenesis of chronic inflammatory diseases, neurodegeneration, and various cancers (Kim & Choi, 2010). Consequently, they have been targeted by numerous small-molecule inhibitors, such as Losmapimod and Tanzisertib, though clinical development has often been hindered by systemic toxicities and the complexity of kinase signaling networks (Hammaker & Firestein, 2010).

Other names

Stress-activated protein kinasesSAPKMAPK8MAPK9MAPK10MAPK11MAPK12MAPK13MAPK14c-Jun N-terminal kinasep38 mitogen-activated protein kinase

Inhibition of kinase activity by competing with ATP for the binding site, thereby preventing the phosphorylation of downstream substrates such as c-Jun, ATF2, and HSP27 (Kyriakis & Avruch, 2012).