PT  - JOURNAL ARTICLE
AU  - Yao, R
AU  - Cooper, GM
TI  - Requirement for phosphatidylinositol-3 kinase in the prevention of apoptosis by nerve growth factor
AID  - 10.1126/science.7701324
DP  - 1995 Mar 31
TA  - Science
PG  - 2003--2006
VI  - 267
IP  - 5206
4099  - http://science.sciencemag.org/content/267/5206/2003.short
4100  - http://science.sciencemag.org/content/267/5206/2003.full
SO  - Science1995 Mar 31; 267
AB  - Nerve growth factor (NGF) induces both differentiation and survival of neurons by binding to the Trk receptor protein tyrosine kinase. Although Ras is required for differentiation, it was not required for NGF-mediated survival of rat pheochromocytoma PC-12 cells in serum-free medium. However, the ability of NGF to prevent apoptosis (programmed cell death) was inhibited by wortmannin or LY294002, two specific inhibitors of phosphatidylinositol (Pl)-3 kinase. Moreover, platelet-derived growth factor (PDGF) prevented apoptosis of PC-12 cells expressing the wild-type PDGF receptor, but not of cells expressing a mutant receptor that failed to activate Pl-3 kinase. Cell survival thus appears to be mediated by a Pl-3 kinase signaling pathway distinct from the pathway that mediates differentiation.