Ligand binding to the AMP-activated protein kinase active site mediates protection of the activation loop from dephosphorylation.

ABSTRACT: The AMP-activated protein kinase (AMPK) is a conserved signaling molecule in a pathway that maintains adenosine triphosphate homeostasis. Recent studies have suggested that low energy adenylate ligands bound to one or more sites in the γ subunit of AMPK promote the formation of an active, phosphatase-resistant conformation. We propose an alternative model in which the kinase domain association with the heterotrimer core results in activation of the kinase catalytic activity, whereas low energy adenylate ligands bound in the kinase active site promote phosphatase resistance. Purified Snf1 α subunit with a conservative, single amino acid substitution in the kinase domain is protected from dephosphorylation by adenosine diphosphate in the complete absence of the β and γ subunits. Staurosporin

SUBMITTER: Chandrashekarappa DG 

PROVIDER: S-EPMC3537075 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature