Recent developments in the structure, function and regulation of platelet-derived growth factor and its receptors

Recent evidence strongly suggests that production of platelet-derived growth factor (PDGF) is regulated by several mechanisms, including noncoordinate expression of the PDGF A- and B-chain genes, alternative transcript splicing, differential mRNA stability, and translational control. Considerable progress has also been made in our understanding of PDGF receptors. Recent studies demonstrate that there are two distinct PDGF receptor genes. PDGF receptors can undergo dimerization and it has been postulated that dimerization can lead to the formation of three different receptor dimers. In addition, it appears that dimerization is required for activation of PDGF receptors and the biological activity of PDGF. Although relatively little is known about the regulation of PDGF receptors, PDGF receptors are known to be down regulated by PDGF, and expression of PDGF receptors begins relatively early during embryogenesis. Furthermore, the binding of PDGF is regulated by cell density. Unexpectedly, recent evidence suggests that PDGF can localize to the nucleus, which suggests an intranuclear function for PDGF may exist. Together, these findings imply a complex and multi-leveled regulatory scheme for controlling the production of PDGF and its receptors.