Role of alpha beta receptor heterodimer formation in beta platelet-derived growth factor (PDGF) receptor activation by PDGF-AB.
We investigated the ability of highly purified recombinant platelet-derived growth factor (PDGF) AB to interact with the products of alpha and beta receptor genes expressed in cells independently or concurrently. Although PDGF-AB lacked any detectable ability to bind or activate beta receptors in cells expressing only this receptor, efficient beta receptor activation by this ligand was readily observed in cells coexpressing alpha platelet-derived growth factor receptors (alpha PDGFRs). beta receptor activation induced by PDGF-AB was shown to be dependent upon in vivo physical association of this receptor with alpha PDGFRs. Moreover, cross-linking analysis established the existence of PDGF-AB-induced beta PDGFR dimers in vivo. All of these findings argue that initial PDGF-AB interaction with the alpha PDGFR induces conformational changes in the ligand or receptor that facilitates efficient recruitment of beta PDGFR by this PDGF isoform.
Heidaran
M A
MA
Laboratory of Cellular and Molecular Biology, National Cancer Institute, Bethesda, Maryland 20892.
Pierce
J H
JH
Yu
J C
JC
Lombardi
D
D
Artrip
J E
JE
Fleming
T P
TP
Thomason
A
A
Aaronson
S A
SA
D000818:Animals; D003432:Cross-Linking Reagents; D004591:Electrophoresis, Polyacrylamide Gel; D004926:Escherichia coli / Q000235:genetics; D005798:Genes, Bacterial; D006801:Humans; D051379:Mice; D008934:Mitogens; D010982:Platelet-Derived Growth Factor / Q000378:metabolism*; D011233:Precipitin Tests; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D017479:Receptors, Platelet-Derived Growth Factor; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D014162:Transfection
D003432:Cross-Linking Reagents; D008934:Mitogens; D010982:Platelet-Derived Growth Factor; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; D017479:Receptors, Platelet-Derived Growth Factor