The stimulation of paracrine and autocrine mitogenic pathways by the platelet-derived growth factor receptor

Platelet-derived growth factor (PDGF) and PDGF-like polypeptides stimulate cell proliferation through paracrine and autocrine pathways. Each of these pathways is mediated by the PDGF receptor. Recently, cDNA clones for the receptor have been isolated and sequenced. The receptor gene on chromosome 5 is transcribed into a single 5.2 kb mRNA. The translated product, which is processed through at least one identifiable precursor, is expressed at the cell surface and is rapidly degraded. When activated by PDGF, the receptor mediates a group of diverse intracellular reactions. The receptor domains that mediate tyrosine kinase activity can be identified in the amino acid sequence of the receptor. However, the domains that mediate other PDGF-stimulated responses, such as turnover of phosphatidylinositol and enhanced expression of the c-myc and c-fos genes, have not been determined. Recently, a full-length receptor cDNA clone has been expressed in cells that normally lack PDGF receptors. This expression system should provide an approach to studies of the function of specific receptor domains and should help determine the relationship among the intracellular reactions stimulated by PDGF.