ERK Allosteric Activation: The Importance of Two Ordered Phosphorylation Events.

ABSTRACT: ERK, a coveted proliferation drug target, is a pivotal kinase in the Ras/ERK signaling cascade. Despite this, crucial questions about its activation have not been fully explored on the foundational, conformational level. Such questions include (i) Why ERK's activation demands dual phosphorylation ; (ii) What is the role of each phosphorylation site in the activation loop ; and (iii) Exactly how the (ordered) phosphorylation steps affect the conformational ensembles of the activation loop , their propensities and restriction to a narrower range favoring ERK's catalytic action . Here we used explicit molecular dynamics simulations to study ERK's stability and the conformational changes in different stages along the activation process. The initial monophosphorylati

SUBMITTER: Regev C 

PROVIDER: S-EPMC12190743 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature