Platelet-derived growth factor-inducible genes respond differentially to at least two distinct intracellular second messengers

Abstract

Platelet-derived growth factor (PDGF) stimulates expression of the c-myc, c-fos, JE, and KC genes in BALB/c/3T3 cells. Here we show that these genes respond differentially to at least two distinct intracellular second messengers generated by PDGF. A broad body of data support the view that response of the c-myc and c-fos genes to PDGF is channeled, at least in part, through activation of protein kinase C. Both PDGF and protein kinase C agonists stimulate transcription of c-myc and c-fos. Down regulation of protein kinase C inhibits the transcriptional induction of c-fos and c-myc by PDGF. In contrast, protein kinase C agonists do not stimulate transcription of JE and KC. Down regulation of protein kinase C does not inhibit the ability of PDGF to stimulate transcription of JE and KC. The differential response of these four genes to PDGF and 12-O-tetradecanoylphorbol-13-acetate correlates with differential phosphorylation of specific intracellular proteins. PDGF treatment stimulates phosphorylation of intracellular proteins at 31, 32, and 80 kilodaltons. Down regulation of protein kinase C prevents phosphorylation of the 80-kDa protein in response to PDGF, but phosphorylation of the smaller proteins is not affected. Finally, PDGF which induces all four genes (and stimulates phosphorylation of three proteins) is a much more potent mitogen than protein kinase C agonists which regulate only some of these events.