REGULATION OF NEURONAL SURVIVAL BY THE SERINE-THREONINE PROTEIN-KINASE AKT

A signaling pathway was delineated by which insulin-like growth factor 1 (IGF-1) promotes the survival of cerebellar neurons. IGF-1 activati on of phosphoinositide 3-kinase (PI3-K) triggered the activation of tw o protein kinases, the serine-threonine kinase Akt and the p70 ribosom al protein S6 kinase (p70(S6K)). Experiments with pharmacological inhi bitors, as well as expression of wild-type and dominant-inhibitory for ms of Akt, demonstrated that Akt but not p70(S6K) mediates PI3-K-depen dent survival. These findings suggest that in the developing nervous s ystem, Akt is a critical mediator of growth factor-induced neuronal su rvival.