Requirement for Phosphatidylinositol-3 Kinase in the Prevention of Apoptosis by Nerve Growth Factor

American Association for the Advancement of Science (AAAS) - Tập 267 Số 5206 - Trang 2003-2006 - 1995
Ryoji Yao1, Geoffrey M. Cooper1
1Division of Molecular Genetics, Dana-Farber Cancer Institute and Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.

Tóm tắt

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 (PI)-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 PI-3 kinase. Cell survival thus appears to be mediated by a PI-3 kinase signaling pathway distinct from the pathway that mediates differentiation.

Từ khóa


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YAO R unpublished data.