Protein kinases mediate basic fibroblast growth factor's stimulation of proliferation and c-fos induction in oligodendrocyte progenitors.
Primary culture was used to examine the effects of basic fibroblast growth factor (bFGF) on oligodendrocyte progenitor proliferation and c-fos expression. Basic FGF induced proliferation approximately six fold. This increased DNA synthesis could be blocked both with genistein, a tyrosine kinase inhibitor, and H-7, a protein kinase C (PKC) inhibitor. These results indicate that protein tyrosine kinase activity and protein kinase C are involved in mediating oligodendrocyte progenitor proliferation. The protooncogene c-fos was investigated as a likely proliferation mediator. Firstly, optimal conditions for bFGF-induced c-fos expression were determined. The oncogene responded maximally between 30 and 60 min of bFGF stimulation. Induction in response to bFGF occurred at 1 ng/ml, increased in a concentration-dependent manner and was maximal at 50 ng/ml. H-7 (50 microM) and genistein (100 microM) blocked c-fos induction as did PKC down-regulation with chronic treatment of phorbol 12-myristate 13-acetate. These results indicate that bFGF induces c-fos expression through receptor tyrosine phosphorylation and PKC activation. Thus similar early signals lead to bFGF-driven proliferation and c-fos induction suggesting a link between these two processes.
Department of Pharmacology and Therapeutics, McGill University, Montreal, Que., Canada.
M
M
Radhakrishna
G
G
Almazan
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000818:Animals; D000831:Animals, Newborn; D015415:Biomarkers; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D001933:Brain Stem / Q000166:cytology / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects*; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects*; D016762:Genes, fos / Q000187:drug effects / Q000502:physiology*; D019833:Genistein; D007150:Immunohistochemistry; D007529:Isoflavones / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D007700:Kinetics; D009836:Oligodendroglia / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors; D014638:Vanadates / Q000494:pharmacology
D015415:Biomarkers; D007529:Isoflavones; D007546:Isoquinolines; D010879:Piperazines; D016222:Fibroblast Growth Factor 2; D014638:Vanadates; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D004247:DNA; D019833:Genistein; D011494:Protein Kinases; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate