Mechanism of platelet-derived growth factor (PDGF) AA, AB, and BB binding to alpha and beta PDGF receptor.

Article Details


Fretto LJ, Snape AJ, Tomlinson JE, Seroogy JJ, Wolf DL, LaRochelle WJ, Giese NA

Mechanism of platelet-derived growth factor (PDGF) AA, AB, and BB binding to alpha and beta PDGF receptor.

J Biol Chem. 1993 Feb 15;268(5):3625-31.

PubMed ID
7679113 [ View in PubMed

The biological effects of platelet-derived growth factor (PDGF) are mediated by cell surface alpha and beta PDGF receptors, which, as a result of ligand binding, undergo dimerization in a manner consistent with PDGF being bivalent. In order to directly demonstrate PDGF bivalency and to define the binding of PDGF AB to isolated beta receptor, we developed solid-phase binding assays using purified recombinant extracellular domain of human PDGF receptors. PDGF AA, AB, and BB were prepared from the monomeric chains expressed in Escherichia coli, and each was purified to homogeneity; PDGF AB contained < 0.5% of either homodimer. The interactions of these isoforms with immobilized PDGF receptors were examined by several approaches. Scatchard analysis revealed high affinity binding (Kd = 0.5-1.0 nM) of radiolabeled PDGF AA and AB to alpha receptor and of PDGF BB to both receptor subtypes. Contrary to previous reports, PDGF AB also bound beta receptor with high affinity (Kd = 0.9 nM). When a B-chain-specific monoclonal antibody that recognizes the putative binding domain of PDGF BB was used for ligand detection, we found that PDGF AB binding to beta receptor occurred exclusively through the B-chain subunit, whereas binding to alpha receptor occurred through either subunit. In addition, site-directed mutagenesis was used to specifically inactivate the B chain of PDGF AB, which eliminated binding to the beta receptor without affecting alpha receptor binding. These results establish that PDGF is bivalent and that monovalent ligand retains high affinity receptor binding.

DrugBank Data that Cites this Article

NameUniProt ID
Platelet-derived growth factor receptor betaP09619Details
Platelet-derived growth factor receptor alphaP16234Details