Role of Glycogen Synthase Kinase-3 in the Phosphatidylinositol 3-Kinase/Akt Cell Survival Pathway
Journal of Biological ChemistryPublished 1 August 1998Open access
Marianna Pap, Geoffrey M. Cooper
Citations1,042
SJR quartileQ1
SJR score1.71
SNIP1.00
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TL;DR
Glycogen synthase kinase-3 plays a critical role in regulation of apoptosis and represents a key downstream target of the PI 3-kinase/Akt survival signaling pathway.
Abstract
Growth factor-dependent survival of a variety of mammalian cells is dependent on the activation of phosphatidylinositol (PI) 3-kinase and its downstream effector, the protein kinase Akt. Glycogen synthase kinase-3 (GSK-3) has been previously identified as a physiological target of Akt, which is inhibited by phosphorylation, so we have investigated the role of GSK-3 in cell survival. Overexpression of catalytically active GSK-3 induced apoptosis of both Rat-1 and PC12 cells, whereas dominant-negative GSK-3 prevented apoptosis following inhibition of PI 3-kinase. GSK-3 thus plays a critical role in regulation of apoptosis and represents a key downstream target of the PI 3-kinase/Akt survival signaling pathway.
Keywords
Biochemistry, Genetics and Molecular Biology
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