ANALYSIS OF PDGF RECEPTOR ROLE IN NEOPLASTIC TRANSFORMATION

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We identified a genomic sequence and cloned the cDNA of a novel receptor-like gene of the platelet-derived growth factor (PDGF) receptor colony-stimulating factor-1 (CSF-1) receptor subfamily. The gene recognized a 6.4-kb transcript that was coexpressed in normal human tissues with the 5.3-kb PDGF receptor mRNA. The expression of its cDNA in COS-1 cells led to the specific binding by 125 I-human PDGF which was competed by all three PDGF isoforms. Expression of the known PDGF receptor cDNA in COS-1 cells led to PDGF binding with a distinct pattern of competition by the same PDGF isoforms. The existence of genes encoding two PDGF receptors that interact in a distinct manner with three different PDGF isoforms likely confers considerable regulatory flexibility in the functional response to PDGF. In order to investigate the functional responses specific to each receptor, we undertook efforts to express their cDNAs in cells normally devoid of either receptor. We demonstrated both that receptors can function in such cells and that each independently mediates major known PDGF activities including mitogenic signal transduction, chemotaxis and stimulation of phosphoinositide turnover. Their binding by different PDGF isoforms distinguishes the two receptor gene products functionally and establishes the newly identified alpha PDGF receptor as the preferred for human PDGF.