A unique autophosphorylation site in the platelet-derived growth factor alpha receptor from a heterodimeric receptor complex

• The platelet-derived growth factor (PDGF) alpha and beta 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 alpha receptor and the beta receptor at comparable levels, to investigate the properties of the alpha beta-heterodimeric receptor complex. PDGF-AB, which mainly induced alpha beta-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 beta 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 alpha receptor was found to be phosphorylated at an additional tyrosine residue, Tyr754, in the heterodimeric complex as compared to the alpha alpha receptor homodimer. Phosphorylation of this tyrosine residue could permit the binding of a specific signal-tranducing protein. A candidate is a 134,000-M(r) protein, which was shown to associate preferentially with the alpha receptor in the heterodimeric receptor complex. It is possible that phosphorylated Tyr754 in the alpha receptor mediates activation of specific signal-tranducing molecules like the 134,000-M(r) substrate, and thereby initiates signal-tranduction pathways from the alpha beta receptor heterodimer, which are distinct from those initiated via homodimeric receptor complexes.

Nyckelord

Amino Acid Sequence

Animals

Aorta

Binding Sites

Cells; Cultured

Endothelium; Vascular/cytology/drug effects/*metabolism

Humans

Kinetics

Macromolecular Substances

Molecular Sequence Data

Phosphates/metabolism

Phosphopeptides/chemistry/isolation & purification

Phosphorylation

Phosphotyrosine

Platelet-Derived Growth Factor/metabolism/*pharmacology

Receptor; Platelet-Derived Growth Factor alpha

Receptor; Platelet-Derived Growth Factor beta

Receptors; Platelet-Derived Growth Factor/*chemistry/*metabolism

Recombinant Proteins/chemistry/metabolism

Research Support; Non-U.S. Gov't

Swine

Transfection

Tyrosine/analogs & derivatives/analysis

MEDICINE

MEDICIN

Publikations- och innehållstyp

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