Dual-Action Kinase Inhibitors Influence p38α MAP Kinase Dephosphorylation.

ABSTRACT: Reversible protein phosphorylation directs essential cellular processes including cell division, cell growth, cell death, inflammation, and differentiation. Because protein phosphorylation drives diverse diseases, kinases and phosphatases have been targets for drug discovery, with some achieving remarkable clinical success. Most protein kinases are activated by phosphorylation of their activation loops, which shifts the conformational equilibrium of the kinase towards the active state. To turn off the kinase, protein phosphatases dephosphorylate these sites, but how the conformation of the dynamic activation loop contributes to dephosphorylation was not known. To answer this, we modulated the activation loop conformational equilibrium of human p38α ΜΑP kinase with existing kinase inhibitor

SUBMITTER: Stadnicki EJ 

PROVIDER: S-EPMC11326130 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature