Abstract Threadgill 9729645 The ERB proteins are a family consisting of four different cell surface receptors with enzymatic kinase activity that are activated by extracellular peptide growth factors. Upon activation these receptors homodimerize with an identical family member or heterodimerize with a different family member transactivating their respective dimerization partner by phosphorylation. These phosphorylated dimers form active signaling complexes that transmit the extracellular signal into the cell. A considerable amount of signaling specificity potentially exists in the type of receptor dimer that is formed. In this grant molecular and genetic analyses will be used to investigate the importance of receptor homo vs heterodimerization in determining signaling specificity and to determine to what extent receptor kinase activity is required for signal transmission. First the mode of receptor phosphorylation will be established in an in vitro cell culture system. The importance of the kinase activity of ERB2 and ERB4 will be studied in an in vivo animal system by engineering specific kinase-inactivating mutations in mice. The experiments will indicate how tyrosine kinase activation influences receptor dimerization and signaling specificity. This research is looking at some cell surface receptors, and studying their early reaction to substances which bind to them, and the means by which they pass this information on to other pathways in the cell which bring about a final response. ***
