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

The p38 mitogen–activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK) pathways are two major branches of the stress-responsive mitogen–activated protein kinases superfamily. Both are serine/threonine kinases activated by various cellular stresses—including cytokines, ultraviolet irradiation, heat shock, osmotic shock—and play key roles in regulating apoptosis, cell differentiation, immune responses, inflammation, and adaptation to environmental changes. The mammalian p38 family includes four main isoforms: α (MAPK14), β (MAPK11), γ (MAPK12/ERK6), δ (MAPK13/SAPK4). The JNK family consists of at least ten isoforms derived from three genes via alternative splicing. These kinases act through phosphorylation cascades that ultimately regulate transcription factors such as ATF2 or c-Jun. Persistent activation is implicated in diseases like cancer and chronic inflammatory conditions; thus both have been explored as therapeutic targets using small-molecule inhibitors that block their catalytic activity or upstream activators. "Both JNKs and p38s are responsive to stress stimuli...and are involved in adaptation to stress, apoptosis or cell differentiation." "The p38 MAPKs are responsive to stress stimuli...and are involved in cell differentiation, apoptosis and autophagy." Note on correctness: This entry combines two related but distinct molecular families; for precise structured data collection it is recommended they be split into separate entries for "p38 mitogen–activated protein kinase" and "c-Jun N-terminal kinase".

Other names

p38 MAPK pathwayJNK pathwayStress-activated protein kinase pathwaysSAPK/JNK (for JNK)

Inhibition of phosphorylation activity to block downstream stress/inflammatory signaling