Mechanism of action and in vivo role of platelet-derived growth factor

Platelet-derived growth factor (PDGF) is a major mitogen for connective tis sue cells and certain other cell ty pes. It is a dimeric molecule consistin g of disulfide-bonded, structurally similar A- and B-polypeptide chains, wh ich combine to homo- and heterodimers. The PDGF isoforms exert their cellul ar effects by binding to and activating two structurally related protein ty rosine kinase receptors, denoted the alpha-receptor and the beta-receptor. Activation of PDGF receptors leads to stimulation of cell growth, but also to changes in cell shape and motility; PDGF induces reorganization of the a ctin filament system and stimulates chemotaxis, i.e., a directed cell movem ent toward a gradient of PDGF. In vivo, PDGF has important roles during the embryonic development as well as during wound healing. Moreover, overactiv ity of PDGF has been implicated in several pathological conditions. The sis oncogene of simian sarcoma virus (SSV) is related to the B-chain of PDGF, and SSV transformation involves autocrine stimulation by a PDGF-like molecu le. Similarly, overproduction of PDGF may be involved in autocrine and para crine growth stimulation of human tumors. Overactivity of PDGF has, in addi tion, been implicated in nonmalignant conditions characterized by an increa sed cell proliferation, such as atherosclerosis and fibrotic conditions. Th is review discusses structural and functional properties of PDGF and PDGF r eceptors, the mechanism whereby PDGF exerts its cellular effects, and the r ole of PDGF in normal and diseased tissues.