title: Insulin-like growth factor I regulates G2/M progression through mammalian target of rapamycin signaling in oligodendrocyte progenitors.
abstract: Extrinsic factors including growth factors influence decisions of oligodendrocyte progenitor cells (OPCs) to continue cell cycle progression or exit the cell cycle and terminally differentiate into oligodendrocytes capable of producing myelin. Multiple studies have elucidated how the G1/S transition is regulated in OPCs; however, little is known about how S phase progression and the G2/M transition are regulated in these cells. Herein, we report that insulin-like growth factor (IGF)-I coordinates with FGF-2 to promote S phase progression but regulates G2/M progression independently. During S phase, IGF-I/FGF-2 enhances protein expression of cyclin A and cdk2, and further increases effective complex formation resulting in enhanced cdk2 activity. Surprisingly, however, OPCs exposed to FGF-2 in the absence of IGF-I fail to traverse through G2/M. Consistent with this observation, OPCs exposed to IGF-I, but not FGF-2, increase cell number over 48 h. IGF-I enhances cdk1 kinase activity during G2/M by promoting nuclear localization of cyclin B/cdk1 as well as of Cdc25C, an activator of cdk1. IGF-I also induces phosphorylation of histone 3 indicating traverse of cells through mitosis. Finally, we demonstrate that IGF-I-mediated G2/M regulation requires mammalian target of rapamycin activity. These data support an important function for IGF-I in G2/M progression in OPCs.
authors: Department of Neurology and Neuroscience and NJMS Cancer Center, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, New Jersey 07101-1709, USA.
authors: Jungsoo
authors: J
authors: Min
authors: Sukhwinder
authors: S
authors: Singh
authors: Patricia
authors: P
authors: Fitzgerald-Bocarsly
authors: Teresa L
authors: TL
authors: Wood
mesh_terms: D000818:Animals; D016203:CDC2 Protein Kinase / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D058953:Neural Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009836:Oligodendroglia / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010766:Phosphorylation; D016548:Prosencephalon / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D016222:Fibroblast Growth Factor 2; D007334:Insulin-Like Growth Factor I; D058570:TOR Serine-Threonine Kinases; D016203:CDC2 Protein Kinase