PROTEIN-KINASES MEDIATE BASIC FIBROBLAST GROWTH-FACTORS 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 blacked 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 mu M) and genistein (100 mu M) 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-fas 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.