Requirement for phosphatidylinositol 3′-kinase to protect hemopoietic progenitors against apoptosis depends upon the extracellular survival factor

摘要: Hemopoietic growth factors promote survival of progenitor cells by preventing their apoptotic death. Recently, phosphatidylinositol 3'-kinase (PI 3-kinase) has been shown to be integral in the pathway which insulin and nerve factor prevent apoptosis. In this work, we show that IL-3-dependent FDCP-1/Mac-1 murine hemopoietic progenitors express receptors for another factor, insulin-like factor-I (IGF-I), both IL-3 IGF-I stimulate PI 3-kinase activity. We then demonstrate shares with properties significantly promoting proliferation enhancing myeloid at concentrations as low 3 ng/ml. efficiently cell presence inhibitors either RNA synthesis (actinomycin D) or mitosis (mitomycin C), suggesting ligands a process is largely independent synthesis. To determine whether mediates IL-3- IGF-I-induced inhibition apoptosis, were incubated inhibitor, wortmannin. While wortmannin inhibited basal IGF-I- IL-3-induced enzyme activity, it did not affect ability protect from even though abrogated These data activation pleiotropic feature progenitors, prevention apoptosis but 3-kinase. Survival therefore maintained least two different intracellular signaling pathways, one requiring does not.