Differential induction of the c-fos promoter through distinct PDGF receptor-mediated signaling pathways

The multiple isoforms of PDGF induce fibroblastic mitogenesis through two distinct PDGF receptors, α and β. The molecular mechanisms by which these α and β PDGF receptors regulate gene expression are poorly understood. We present data which indicates that differential induction of c‐fos gene expression by PDGF isoforms occurs through distinct PDGF α and β receptor‐mediated signaling pathways. Comparison of PDGF‐AA with PDGF‐BB stimulation showed that PDGF‐BB induced prolonged expression of the c‐fos gene in BALB/c‐3T3 cells, but that PDGF‐AA induced more potent activation of the serum response element (SRE) in transient transfection assays. PDGF‐AA, which binds α but not β PDGF receptors, could only induce the SRE through a protein kinase C (PKC)‐dependent pathway, whereas PDGF‐BB, which binds both α and β PDGF receptors, could also induce the SRE through a PKC‐independent pathway. These results suggest that PDGF α receptors activate the PKC‐dependent signaling pathway while PDGF β receptors also activate a PKC‐independent pathway. In addition, we found that PDGF‐BB could induce another c‐fos promoter element within the — 90 to + 10 region, suggesting that the more potent mitogenic effect and prolonged c‐fos gene expression induced by PDGF‐BB may result from cooperativity between more than one c‐fos promoter elements.