Distinct roles for PI3K in proliferation and survival of oligodendrocyte progenitor cells

Phosphoinositol 3-kinase (P13K) is a downstream effector for multiple ligan d-activated receptors and modulates cell responses through activation of it s target protein kinase B (Akt). We examined the roles of P13K-Akt signalin g in a primary glial (oligodendrocyte) progenitor cell culture system that is ligand-dependent for cell proliferation, survival, and prevention of dif ferentiation. We demonstrate that P13K and Akt (Ser-473 phosphorylation) ar e activated in response to platelet-derived growth factor but not basic fib roblast growth factor-2 (FGF2) and that distinct forms of P13K are activate d in early progenitors and later-maturation pro-oligodendroblasts as identi fied by their sensitivity to wortmannin. By establishing conditions to exam ine effects on cell proliferation and survival independently, we demonstrat e that P13K is necessary for a full mitogenic response and that P13K is als o necessary for early progenitor survival. Our results therefore demonstrat e that P13K-Akt signaling independently regulates proliferation and surviva l, that the form of P13K is distinct in early progenitors and pro-oligodend roblasts, and that FGF2 does not activate this pathway in either primary gl ial cell population. J. Neurosci. Res. 62: 336-345, 2000. (C) 2000 Wiley-Li ss, Inc.