p38 MAPK

p38 MAPK (p38 mitogen-activated protein kinase), comprising four isoforms (α, β, γ, δ) with p38α being the predominant and most studied form, is a stress-activated kinase that is phosphorylated and activated by upstream MAP2Ks (MKK3 and MKK6) in response to inflammatory cytokines, oxidative stress, UV irradiation, and osmotic shock. It phosphorylates a wide range of substrates including the downstream kinase MK2, transcription factors ATF2 and MEF2, and AU-rich element-binding proteins that stabilise pro-inflammatory mRNAs such as TNF-α. In ageing biology, p38α drives the SASP in senescent cells via NF-κB and MK2/tristetraprolin, suppresses satellite cell self-renewal by phosphorylating MyoD and disrupting quiescence, and mediates inflammatory amplification in inflammaging; pharmacological p38α inhibition has been shown to restore muscle regeneration in aged mice.