p38 mitogen-activated protein kinase (MAP kinase) pathway (p38 MAPK pathway)

The p38 mitogen-activated protein kinase (MAPK) pathway is a major stress-activated protein kinase cascade that transduces signals from a variety of extracellular stimuli, including cytokines, ultraviolet light, heat, osmotic shock, and pro-inflammatory signals, to intracellular responses controlling gene expression, cell cycle, apoptosis, and differentiation. There are four main isoforms of p38 MAPK in mammals: p38α (MAPK14), p38β (MAPK11), p38γ (MAPK12), and p38δ (MAPK13), with p38α being the most studied therapeutic target. Persistent or dysregulated activity of this pathway contributes to inflammatory diseases, cancer, and other pathologies, and multiple pharmaceutical agents have been designed to inhibit p38 MAPKs, although clinical success has been limited by safety and efficacy challenges.

Other names

p38 pathwayStress-activated protein kinase pathway (SAPK2a for p38α, SAPK2b for p38β, SAPK3 for p38γ, SAPK4 for p38δ)p38 MAPK signalingCSBP pathway (for p38α, also called Cytokinin Specific Binding Protein)RK pathway

Inhibition of p38 MAPK enzymatic activity, thereby suppressing phosphorylation of downstream kinases and transcription factors, leading to reduced expression of pro-inflammatory cytokines (e.g., TNF-α, IL-1) Blockade of signal transduction cascades mediating inflammatory and stress responses