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Platelet-derived growth factor (PDGF) stimulates PDGF receptor subunit dimerization and intersubunit
J D Kelly1, B A Haldeman, F J Grant
1Department of Pathology, University of Washington, Seattle 98195.
The Journal of Biological Chemistry
|May 15, 1991
Summary
Researchers identified the human platelet-derived growth factor (PDGF) receptor alpha-subunit, detailing its binding affinities for different PDGF isoforms. They also demonstrated that PDGF binding induces receptor dimerization and tyrosine phosphorylation in cells.
Area of Science:
- Molecular Biology
- Cell Signaling
- Receptor Biology
Background:
- Platelet-derived growth factor (PDGF) binding is thought to involve interactions between dimeric PDGF and two receptor subunits: alpha and beta.
- Understanding these interactions is crucial for deciphering PDGF-mediated cellular responses.
Purpose of the Study:
- To clone and characterize the human PDGF receptor alpha-subunit.
- To investigate the binding affinities of different PDGF isoforms to the alpha-subunit.
- To elucidate the role of PDGF binding in receptor dimerization and tyrosine phosphorylation.
Main Methods:
- Cloning and expression of human PDGF receptor alpha-subunit cDNA.
- Scatchard analysis to determine binding affinities.
- Utilizing wild-type and kinase-inactive human beta-subunits in cell-based assays.
Main Results:
- The cloned cDNA corresponds to the PDGF receptor alpha-subunit, exhibiting specific binding properties and antibody recognition.
- High-affinity binding (Kd = 0.05-0.06 nM) was observed for PDGF-AA and PDGF-AB with alpha-subunits.
- PDGF-BB also bound with high affinity (Kd = 0.4 nM) at physiological concentrations.
- PDGF binding was shown to promote receptor subunit dimerization.
- Tyrosine phosphorylation of kinase-inactive beta-subunits occurred when co-expressed with alpha-subunits, at conserved phosphorylation sites.
Conclusions:
- The human PDGF receptor alpha-subunit has been successfully cloned and characterized.
- The alpha-subunit exhibits distinct binding affinities for different PDGF isoforms.
- PDGF binding is a key trigger for receptor dimerization and subsequent tyrosine phosphorylation events, potentially involving intermolecular signaling.