Modulation of GSK3β autoinhibition by Thr-7 and Thr-8.

ABSTRACT: Glycogen synthase kinase 3β (GSK-3β) is a pivotal signaling node that regulates a myriad of cellular functions and is deregulated in many pathological conditions, making it an attractive therapeutic target. Inhibitory Ser-9 phosphorylation of GSK3β by AKT is an important mechanism for negative regulation of GSK3β activity upon insulin stimulation. Here, we report that Thr-7 and Thr-8 residues located in the AKT/PKB substrate consensus sequence on GSK3β are essential for insulin-stimulated Ser-9 phosphorylation in vivo and for GSK3β inactivation. Intestinal cell kinase (ICK) phosphorylates GSK3β Thr-7 in vitro and in vivo. Thr-8 phosphorylation partially inhibits GSK3β, but Thr-7 phosphorylation promotes GSK3β activity and blocks phospho-Ser-9-dependent GSK3β autoinhibition. Our findings un

SUBMITTER: Tong Y 

PROVIDER: S-EPMC5829016 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature