Molecular Localization of the Transforming and Secretory Properties of PDGF A and PDGF B

Human platelet-derived growth factor (PDGF) is a connective tissue cell mitogen comprised of two related chains encoded by distinct genes. The B chain is the homolog of the v-sis oncogene product. Properties that distinguish these ligands include greater transforming potency of the B chain and more efficient secretion of the A chain. By a strategy involving the generation of PDGF A and B chimeras, these properties were mapped to distinct domains of the respective molecules. Increased transforming efficiency segregated with the ability to activate both α and β PDGF receptors. These findings genetically map PDGF B residues 105 to 144 as responsible for conformational alterations critical to β PDGF receptor interaction and provide a mechanistic basis for the greater transforming potency of the PDGF B chain.