Ser500 phosphorylation acts as a conformational switch to prime eEF-2K for activation.

ABSTRACT: Eukaryotic elongation factor-2 kinase (eEF-2K), a member of the α-kinase family of atypical kinases, phosphorylates eukaryotic elongation factor 2 (eEF-2), thereby inhibiting ribosomal translocation and downregulating translational elongation in response to diverse cellular cues. eEF-2K is activated by Ca²⁺/calmodulin (CaM) and integrates upstream inputs from diverse signaling pathways, including PKA and mTOR, which target regulatory sites on a disordered regulatory loop. Among these, serine 500 (S500) has been identified as a key phosphorylation site targeted by both eEF-2K and PKA. However, the influence of this post-translational modification on the properties of eEF-2K has remained unclear. Prior studies have shown that S500 phosphorylation accelerates autophosphorylation of

SUBMITTER: Bohanon AL 

PROVIDER: S-EPMC12236703 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature