RT Journal Article
SR Electronic
T1 Requirement for phosphatidylinositol-3 kinase in the prevention of apoptosis by nerve growth factor
JF Science
JO Science
FD American Association for the Advancement of Science
SP 2003
OP 2006
DO 10.1126/science.7701324
VO 267
IS 5206
A1 Yao, R
A1 Cooper, GM
YR 1995
UL http://science.sciencemag.org/content/267/5206/2003.abstract
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.