Chimeric alpha- and beta-platelet-derived growth factor (PDGF) receptors define three immunoglobulin-like domains of the alpha-PDGF receptor that determine PDGF-AA binding specificity.
Binding of platelet-derived growth factor (PDGF) to its cell surface receptors stimulates a variety of biochemical and biological responses. Two receptor gene products (designated alpha and beta) have been identified, and the different binding affinities of various PDGF isoforms for these receptors are prime determinants of the spectrum of responses observed. The beta receptor binds PDGF-BB, but not PDGF-AA, while the alpha receptor binds PDGF-AA and PDGF-BB. We utilized these different ligand binding specificities to investigate the PDGF-AA binding site in the human alpha-PDGF receptor by constructing chimeric molecules between the human alpha- and beta-PDGF receptors. Our results demonstrate that amino acids 1-340 of the alpha-PDGF receptor comprise the region that confers PDGF-AA binding specificity. This region corresponds to immunoglobulin-like sub-domains 1, 2, and 3 of its external domain.
Heidaran
M A
MA
Laboratory of Cellular and Molecular Biology, National Cancer Institute, Bethesda, Maryland 20892.
Pierce
J H
JH
Jensen
R A
RA
Matsui
T
T
Aaronson
S A
SA
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D001667:Binding, Competitive; D002460:Cell Line; D002678:Chimera; D006412:Hematopoietic Stem Cells; D006801:Humans; D015151:Immunoblotting; D007136:Immunoglobulins / Q000235:genetics*; D007700:Kinetics; D008024:Ligands; D051379:Mice; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D010982:Platelet-Derived Growth Factor / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000378:metabolism; D017479:Receptors, Platelet-Derived Growth Factor; D013379:Substrate Specificity
D007136:Immunoglobulins; D008024:Ligands; D015345:Oligonucleotide Probes; D010982:Platelet-Derived Growth Factor; D011956:Receptors, Cell Surface; D017479:Receptors, Platelet-Derived Growth Factor