Regulation of neuronal survival by the serine-threonine protein kinase Akt

H Dudek, SR Datta, TF Franke, MJ Birnbaum, R Yao… - Science, 1997 - science.org
Science, 1997science.org
A signaling pathway was delineated by which insulin-like growth factor 1 (IGF-1) promotes
the survival of cerebellar neurons. IGF-1 activation of phosphoinositide 3-kinase (PI3-K)
triggered the activation of two protein kinases, the serine-threonine kinase Akt and the p70
ribosomal protein S6 kinase (p70S6K). Experiments with pharmacological inhibitors, as well
as expression of wild-type and dominant-inhibitory forms of Akt, demonstrated that Akt but
not p70S6K mediates PI3-K-dependent survival. These findings suggest that in the …
A signaling pathway was delineated by which insulin-like growth factor 1 (IGF-1) promotes the survival of cerebellar neurons. IGF-1 activation of phosphoinositide 3-kinase (PI3-K) triggered the activation of two protein kinases, the serine-threonine kinase Akt and the p70 ribosomal protein S6 kinase (p70S6K). Experiments with pharmacological inhibitors, as well as expression of wild-type and dominant-inhibitory forms of Akt, demonstrated that Akt but not p70S6K mediates PI3-K-dependent survival. These findings suggest that in the developing nervous system, Akt is a critical mediator of growth factor-induced neuronal survival.
AAAS