Signal Transduction by the Platelet-derived Growth Factor Receptor

When platelet-derived growth factor (PDGF) binds to its receptor on the surface of a mesenchymal cell, it stimulates almost every known type of hormone-activated signal transduction pathway. Within seconds, tyrosine kinase activity is stimulated (Nishimura et al. 1982; Ek et al. 1983; Frackelton et al. 1984), phosphatidylinositol (PtdIns) is hydrolyzed (Habenicht et al. 1981), the cellular pH changes (L'Allemain et al. 1984), and cytosolic calcium increases (Escobedo et al. 1988a). Other rapid responses include dramatic changes in the cytoskeleton, enhanced expression of a group of genes (Kelly et al. 1983; Greenberg and Ziff 1984), elevation in the level of cellular cAMP (Rozengurt et al. 1983), and internalization of the receptor. How these events culminate in DNA synthesis is still unknown. However, recent progress in understanding the structure and function of the PDGF receptor is providing mechanistic insight into the interrelationships among the pathways and their roles in mitogenesis.