A Unique Autophosphorylation Site in the Platelet‐Derived Growth Factor α Receptor from a Heterodimeric Receptor Complex

The platelet‐derived growth factor (PDGF) α and β receptors undergo dimerization as a consequence of ligand binding. Depending on the PDGF isoform (PDGF‐AA, ‐AB or ‐BB), homodimers or heterodimers of receptors are formed. In this study, we have used transfected porcine aortic endothelial cells, coexpressing cDNAs for the α receptor and the β receptor at comparable levels, to investigate the properties of the αβ‐heterodimeric receptor complex. PDGF‐AB, which mainly induced αβ‐heterodimeric complexes, was the most efficient isoform for stimulating mitogenicity. Actin reorganization, in the form of circular membrane ruffling and chemotaxis, was induced by PDGF‐AB and PDGF‐BB, but not by PDGF‐AA, thus indicating that the β receptor in the homodimeric or heterodimeric configuration was required for induction of motility responses. The molecular basis for the apparent receptor dimer‐specific properties was examined by analyzing receptor autophosphorylation and phosphorylation of substrates. The α receptor was found to be phosphorylated at an additional tyrosine residue, Tyr754, in the heterodimeric complex as compared to the αα receptor homodimer. Phosphorylation of this tyrosine residue could permit the binding of a specific signal‐tranducing protein. A candidate is a 134000‐ M r protein, which was shown to associate preferentially with the α receptor in the heterodimeric receptor complex. It is possible that phosphorylated Tyr754 in the α receptor mediates activation of specific signal‐tranducing molecules like the 134000‐ M r substrate, and thereby initiates signal‐tranduction pathways from the αβ receptor heterodimer, which are distinct from those initiated via homodimeric receptor complexes.