Binding of platelet-derived growth factor (PDGF) to its cell surface receptors stimulates a variety of biochemical and biological responses. Two distinct PDGF receptors have been identified and each exhibits different binding affinities for the variant PDGF isoforms. The a PDGFR binds PDGF-AA and PDGF-BB, whereas the beta PDGFR binds PDGF-BB only. We have previously shown that the first three IgG-like loops of alpha PDGFR contains determinants required for its high affinity toward PDGF-AA. In order to further investigate the function of each subdomain localized within the first three IgG-like loops, we have generated deletion mutants of a PDGFR lacking any of the first three subdomains. Our results indicate that each subdomain appears to have a distinct role in PDGFR signalling. Binding of PDGF to its cell surface receptor results in tyrosine phosphorylation of a number of cellular proteins which are thought to be critical for receptor-mediated mitogenic response in vivo. In an attempt to identify novel signalling molecules, we have generated a polyclonal antibody against a partially purified substrate of PDGFR kinase domain. This antibody was subsequently used to identify clones which are currently being characterized.
