In NIH/3T3 cells where both platelet-derived growth factor receptor (PDGFR) subtypes are coexpressed. the higher transforming function of PDGF-BB as compared to that induced by PDGF-AA was shown to be directly linked to distinct substrate specificity of betaPDGFR kinase. Construction and characterization of chimeric molecules between alphaPDGFR and betaPDGFR defined a domain responsible for higher transforming activity of PDGF-BB mediated by betaPDGFR kinase. Construction and characterization of deletion mutants of alphaPDGFR defined a domain responsible for PDGF-A mediated transformation in NIH/3T3 fibroblasts. The role of specific tyrosine mutation within this domain is under investigation. A cotransfection experiment was developed to identify limiting substrates involved in PDGF-A transforming function in NIH/3T3 cells. In cotransfection experiments. the low PDGF-A transforming function was significantly increased by expression constructs represented in a cDNA library of endothelial cells. The identity of these limiting clones are under investigation.
