Distinct roles of GSK-3alpha and GSK-3beta phosphorylation in the heart under pressure overload.

ABSTRACT: Glycogen synthase kinase-3 (GSK-3) is a master regulator of growth and death in cardiac myocytes. GSK-3 is inactivated by hypertrophic stimuli through phosphorylation-dependent and -independent mechanisms. Inactivation of GSK-3 removes the negative constraint of GSK-3 on hypertrophy, thereby stimulating cardiac hypertrophy. N-terminal phosphorylation of the GSK-3 isoforms GSK-3alpha and GSK-3beta by upstream kinases (e.g., Akt) is a major mechanism of GSK-3 inhibition. Nonetheless, its role in mediating cardiac hypertrophy and failure remains to be established. Here we evaluated the role of Serine(S)21 and S9 phosphorylation of GSK-3alpha and GSK-3beta in the regulation of cardiac hypertrophy and function during pressure overload (PO), using GSK-3alpha S21A knock-in (alphaKI) and GSK-3beta

SUBMITTER: Matsuda T 

PROVIDER: S-EPMC2634936 | biostudies-literature | 2008 Dec

REPOSITORIES: biostudies-literature