Signal transduction by the receptors for platelet-derived growth factor.

Platelet-derived growth factor (PDGF) is a connective tissue cell mitogen that originally was purified from human platelets, but recently has been found to be produced by many different cell types (reviewed by Ross et al. 1986; Heldin and Westermark, 1989). The in vivo function of PDGF remains speculative, but the fact that PDGF is released by platelets and by cells involved in the inflammatory reaction and that it stimulates proliferation, chemotaxis and matrix production, suggest a role in tissue repair processes. It is also possible that PDGF is involved in regulation of cell growth and differentiation during embryonal development, since it has been found to be expressed in mouse (Rappolee et al. 1988) and Xenopus (Mercola et al. 1988) embryos and in human placenta (Goustin et al. 1985). Such a function has been demonstrated in the developing rat optic nerve where PDGF secreted by type-1 astrocytes control the differentiation of O-2A progenitor cells into oligodendrocytes and type-2 astrocytes (Noble etal. 1988; Richardson etal. 1988; Raff et al. 1988). PDGF may also be involved in pathological processes. Thus, unscheduled production of PDGF may account for the excessive cell proliferation seen, e.g., in atherosclerosis and tissue fibrosis, as well as in malignancies. The potent transforming activity of PDGF is illustrated by the fact that the PDGF B chain gene is similar to v-sis, the transforming gene of simian sarcoma virus, and that cell transformation by this virus is exerted by autocrine action of a PDGF-like factor (reviewed by Westermark et al. 1987).