p38 and JNK Mitogen-Activated Protein Kinase signaling pathway (p38/JNK signaling)

The p38 and JNK (c-Jun N-terminal kinase) signaling pathways are two major branches of the mitogen-activated protein kinase (MAPK) family, collectively referred to as stress-activated protein kinases (SAPKs). These pathways are primarily triggered by environmental stressors, such as oxidative stress and DNA damage, as well as inflammatory cytokines like tumor necrosis factor (TNF) and interleukin-1 (IL-1). Upon activation, they regulate a wide array of cellular processes, including the production of pro-inflammatory mediators, cell cycle progression, and the induction of apoptosis. In various diseases, particularly chronic inflammatory disorders and cancer, the p38/JNK axis is often dysregulated, contributing to pathological inflammation or therapeutic resistance. Consequently, these kinases have been extensively targeted by small molecule inhibitors in clinical trials for conditions such as rheumatoid arthritis and various solid tumors. However, the dual role of these pathways as both tumor suppressors and promoters, depending on the cellular context, presents a significant challenge for therapeutic development.

Other names

Stress-activated protein kinase signalingSAPK signalingp38/JNK axisStress-activated MAPK signalingp38 MAPK and JNK pathway

Inhibition of the phosphorylation and catalytic activity of p38 and JNK kinase isoforms, thereby blocking the activation of downstream transcription factors (e.g., c-Jun, ATF2) and reducing the production of pro-inflammatory cytokines such as TNF-alpha and IL-1 beta.