Mitogen-activated protein kinase 14 (p38 alpha MAPK) (p38 alpha)

Mitogen-activated protein kinase 14 (MAPK14), widely known as p38 alpha, is a member of the serine/threonine protein kinase family and a key mediator in the p38 MAPK signaling pathway (UniProt P47811). It is activated by a variety of environmental stresses, such as oxidative stress and UV radiation, as well as inflammatory cytokines like tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (PubMed: 10409757). Upon activation, p38 alpha regulates the expression of numerous genes involved in inflammation, cell proliferation, differentiation, and apoptosis by phosphorylating downstream kinases and transcription factors (NCBI Gene: 1432). Due to its central role in cytokine production, p38 alpha has been a major therapeutic target for chronic inflammatory diseases, including rheumatoid arthritis and Crohn's disease, as well as in oncology and neurodegeneration (PubMed: 26011251). While many small-molecule inhibitors have been developed to target its ATP-binding or allosteric sites, clinical progress has been hampered by systemic toxicities and the transient nature of the inhibitory response in some tissues (PubMed: 19143602).

Other names

p38 alphaMAPK14SAPK2ACSBPCSBP1CSBP2CSPB1MXI2PRKM14PRKM15RK

Inhibition of the catalytic activity of p38 alpha by competing with ATP for the binding site or by binding to an allosteric site that stabilizes an inactive conformation (PubMed: 19143602).