1. The role of the juxtamembrane domain in mediating erbB-2 on EGFR- profile mitogenic signals was analyzed. A number of bioassays which readily distinguish between the mitogenic properties of erbB-2 and EGFR was developed. Results indicate that a single amino acid change in corresponding position of the EGFR and erbB-2 (Arg 662 in EGFR and Thr 694 in erbB-2) is responsible for most of the differences in mitogenic signalling between these two molecules. 2. Cloning and characterization of novel substrates for the epidermal growth factor receptors were undertaken. At least three novel substrates for the EGFR kinase were discovered: eps10, eps8 and eps15 (eps is an acronym for EGFR-pathway substrates). Molecular analyses show that eps10 encodes for radixin, a member of an expanding family of band 4.1-related proteins. Eps8 encodes for a protein bearing the characteristic hallmarks of kinase substrates, i.e., SH2 and SH3 domains. The characterization of eps is still pending.
