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 alpha and beta PDGF receptors. These findings genetically map PDGF B residues 105 to 144 as responsible for conformational alterations critical to beta PDGF receptor interaction and provide a mechanistic basis for the greater transforming potency of the PDGF B chain.
LaRochelle
W J
WJ
Laboratory of Cellular and Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
Giese
N
N
May-Siroff
M
M
Robbins
K C
KC
Aaronson
S A
SA
D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic; D002678:Chimera; D005822:Genetic Vectors; D006801:Humans; D008024:Ligands; D010982:Platelet-Derived Growth Factor / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D011233:Precipitin Tests; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000502:physiology; D020574:Proto-Oncogene Proteins c-sis; D011956:Receptors, Cell Surface / Q000235:genetics; D017479:Receptors, Platelet-Derived Growth Factor; D014162:Transfection
D008024:Ligands; D010982:Platelet-Derived Growth Factor; D011518:Proto-Oncogene Proteins; D020574:Proto-Oncogene Proteins c-sis; D011956:Receptors, Cell Surface; D017479:Receptors, Platelet-Derived Growth Factor