Platelet-derived growth factor generates at least two distinct intracellular signals that modulate gene expression

Regulation of the genes by PDGF has some common features. All are primary response genes, and they can still be expressed in the presence of cycloheximide (Cochran et al. 1983; Kelly et al. 1983; Kruijer et al. 1984; Lau and Nathans 1985). In fact, many of the genes are superinduced when cells are treated with growth factors plus cycloheximide (Greenberg et al. 1986). The genes that have been characterized all contain a sequence motif in their 3'-noncoding sequences that appears to make the message labile (Meijlink et al. 1985; Treisman 1985; Shaw and Kamen 1986). All competence genes so far examined are controlled at least in part at the level of transcription (Cochran et al. 1983; Edwards et al. 1985; Almendral et al. 1988). Differences in regulation of the genes include variations in the time course of induction, ranging from 10 minutes to over 4 hours, and differences in the persistence of the mRNAs after their synthesis (Cochran et al. 1983; Muller et al. 1984; Lau and Nathans 1987). The data presented in this paper strongly suggest that multiple, distinct intracellular signals that lead to the expression of multiple genes are generated when cells are treated with growth factors such as PDGF. The variation in the time course of induction of PDGF-inducible genes suggests several models of signal transduction. Four such models are presented in Figure 5. One possibility (Fig. 5A) is that one signal is generated by the interaction of PDGF with its receptor and that this signal activates the very early genes, such as c-fos.(ABSTRACT TRUNCATED AT 250 WORDS)