Ligand-induced homo- and hetero-dimerization of platelet-derived growth factor alpha- and beta-receptors in intact cells.

Porcine aortic endothelial cells expressing platelet-derived growth factor (PDGF) alpha- or beta-receptors after transfection of the corresponding cDNAs, were used to investigate whether PDGF receptor dimerization occurs in intact cells after ligand binding. Using three different methods--covalent cross-linking of 125I-labeled ligand, cross-linking of metabolically labeled cells after ligand-binding followed by immunoprecipitation, and immunoblotting of cells after ligand binding and cross-linking--it was demonstrated that alpha- as well as beta-receptors form ligand-induced dimeric complexes. Dimerization correlated with induction of receptor kinase activity, measured as receptor autophosphorylation. Heterodimeric complexes could furthermore be induced by PDGF-AB, when added to a mixture of lysates from the alpha- and beta-receptor expressing cell lines, or when added to human fibroblasts which express both receptor types.