M. Pap et Gm. Cooper, ROLE OF GLYCOGEN-SYNTHASE KINASE-3 IN THE PHOSPHATIDYLINOSITOL 3-KINASE AKT CELL-SURVIVAL PATHWAY/, The Journal of biological chemistry, 273(32), 1998, pp. 19929-19932
Growth factor-dependent survival of a variety of mammalian cells is de
pendent on the activation of phosphatidylinositol (PI) 3-kinase and it
s downstream effector, the protein kinase Akt. Glycogen synthase kinas
e-3 (GSK-3) has been previously identified as a physiological target o
f Akt, which is inhibited by phosphorylation, so we have investigated
the role of GSK-3 in cell survival. Overexpression of catalytically ac
tive GSK-3 induced apoptosis of both Rat-1 and PC12 cells, whereas dom
inant-negative GSK-3 prevented apoptosis following inhibition of PI 3-
kinase. GSK-3 thus plays a critical role in regulation of apoptosis an
d represents a key downstream target of the PI 3-kinase/Akt survival s
ignaling pathway.