Distinct roles for PI3K in proliferation and survival of oligodendrocyte progenitor cells
Autor: | Sylvie Ebner, Randall D. McKinnon, Maryse Dunbar |
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Rok vydání: | 2000 |
Předmět: |
Platelet-derived growth factor
Cell Survival Protein Serine-Threonine Kinases Ligands Fibroblast growth factor Rats Sprague-Dawley Phosphatidylinositol 3-Kinases Cellular and Molecular Neuroscience chemistry.chemical_compound Proto-Oncogene Proteins medicine Animals Enzyme Inhibitors Phosphorylation Progenitor cell Protein kinase B Cells Cultured PI3K/AKT/mTOR pathway Platelet-Derived Growth Factor Phosphoinositide 3-kinase biology Cell growth Stem Cells Oligodendrocyte Rats Cell biology Androstadienes Oligodendroglia medicine.anatomical_structure chemistry biology.protein Fibroblast Growth Factor 2 Wortmannin Proto-Oncogene Proteins c-akt Cell Division Signal Transduction |
Zdroj: | Journal of Neuroscience Research. 62:336-345 |
ISSN: | 1097-4547 0360-4012 |
DOI: | 10.1002/1097-4547(20001101)62:3<336::aid-jnr3>3.0.co;2-h |
Popis: | Phosphoinositol 3-kinase (PI3K) is a downstream effector for multiple ligand-activated receptors and modulates cell responses through activation of its target protein kinase B (Akt). We examined the roles of PI3K-Akt signaling in a primary glial (oligodendrocyte) progenitor cell culture system that is ligand-dependent for cell proliferation, survival, and prevention of differentiation. We demonstrate that PI3K and Akt (Ser-473 phosphorylation) are activated in response to platelet-derived growth factor but not basic fibroblast growth factor-2 (FGF2) and that distinct forms of PI3K are activated in early progenitors and later-maturation pro-oligodendroblasts as identified by their sensitivity to wortmannin. By establishing conditions to examine effects on cell proliferation and survival independently, we demonstrate that PI3K is necessary for a full mitogenic response and that PI3K is also necessary for early progenitor survival. Our results therefore demonstrate that PI3K-Akt signaling independently regulates proliferation and survival, that the form of PI3K is distinct in early progenitors and pro-oligodendroblasts, and that FGF2 does not activate this pathway in either primary glial cell population. |
Databáze: | OpenAIRE |
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