Differences in signal transduction pathways by which platelet-derived and fibroblast growth factors activate extracellular signal-regulated kinase indifferentiating oligodendrocytes

Treatment of cultured rat oligodendroglial progenitors with either platelet -derived growth factor (PDGF) or fibroblast growth factor-2 (FGF-2) activat ed extracellular signal regulated kinase 2 (ERK2). Activation was transient in response to PDGF, whereas it was greater and more prolonged in response to FGF-2. ERK2 activation by PDGF was preceded by a very rapid, robust and transient tyrosine phosphorylation of the PDGF receptor. Although there wa s consistently more activation of ERK2 in response to FGF-2 than to PDGF, i mmunostaining of FGF receptors 1 (FGFR1) and 2 (FGFR2) and their tyrosine p hosphorylation in progenitors was very weak, and both receptors were up-reg ulated during differentiation to oligodendrocytes. Tyrosine phosphorylation of the FGF receptors was maximal from 15 to 60 min of treatment and was su stained for many hours. Binding of radioiodinated FGF-2 to FGFR1 was predom inant in progenitors, whereas binding to FGFR2 was predominant in oligodend rocytes. ERK2 activation by PDGF was more sensitive to inhibition of tyrosi ne kinases, whereas ERK2 activation by FGF-2 was relatively more sensitive to inhibitors of protein kinase C. These differences in signal-transduction pathways probably contribute to the different cellular responses of oligod endroglial lineage cells to PDGF and FGF-2, respectively.