Platelet-derived growth factor receptor: current views of the two-subunit model.
Platelet-derived growth factor (PDGF) has been identified as a major mitogen in serum for cultured cells of mesenchymal origin. PDGF was first identified in and purified from human platelet sources. PDGF from platelets is composed of two chains, A-chains and B-chains, which share 60% sequence identity and which can dimerize to form the three combinations PDGF-AA, PDGF-BB, and PDGF-AB. All three dimer forms of PDGF have been isolated from natural sources. Initial studies involving PDGF were based upon the existence of a single cell-surface receptor for PDGF. It has recently been demonstrated that there are two PDGF-receptor subunits, termed alpha and beta, which can associate as three dimer forms (alpha/alpha, alpha/beta, beta/beta) with variable binding specificity for the PDGF ligand dimers. cDNA clones have been obtained for both of the receptor subunits and were shown to code for similar proteins belonging to the split tyrosine kinase family of receptors. The current model of the PDGF receptor subunits proposes that high-affinity binding sites require dimerization of the subunits and that dimerization is associated with activation of the tyrosine kinase of the receptors. The total number of the two receptor subunits and ratio expressed varies between cell types and appears to account for the variable responsiveness of different cell types to the three dimer forms of PDGF.
Hart
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ZymoGenetics Inc., University of Washington, Seattle 98105.
Bowen-Pope
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D000595:Amino Acid Sequence; D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D004247:DNA / Q000235:genetics; D006801:Humans; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D017479:Receptors, Platelet-Derived Growth Factor; D014018:Tissue Distribution
D010982:Platelet-Derived Growth Factor; D011956:Receptors, Cell Surface; D004247:DNA; D017479:Receptors, Platelet-Derived Growth Factor