METABOLISM OF THE EGF-RECEPTOR AND ERBB PROTEIN

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Studies of the metabolism of the epidermal growth factor (EGF) receptor and the erbB protein will continue. These studies should contribute to the understanding of some of the mechanisms involved in regulation of cell division in higher organisms. The relationship between EGF receptor and erbB protein mediated mitogenesis and phosphorylation of proteins on tyrosine residues will be examined using antibodies against these proteins and anti-phosphotyrosine antibodies. The effects of in vivo tyrosine phosphorylation of the EGF receptor and erbB protein on their respective activities will be determined. Anti-phosphotyrosine antibodies will be used to isolate tyrosine phosphorylated proteins from EGF treated cells and avian erythroblastosis virus (AEV) transformed cells. These proteins may play a role in triggering cell division. Particular attention will be paid to the identification of tyrosine phosphorylated membrane proteins and proteins which associate with the tyrosine phosphorylated forms of the EFG receptor and erbB proteins. The mechanism through which tumor promoters attenuate mitogenic signalling of the EGF receptor and erbB protein will be approached. The effects of tumor promoters on tyrosine phosphorylation of proteins will be determined. Cells will be transformed by AEV containing erbB protein mutated at or near threonine 98 (which is phosphorylated in response to tumor promoter treatment of cells). These cells will be assessed for altered responses to tumor promoters. The effects of platelet derived growth factor on EGF receptor function will also be investigated. The metabolism of carboxy terminus truncated erbB protein versus full length carboxy terminus erbB protein will be studied with respect to biosynthesis, turnover, intracellular localization, kinase activity and oncogenicity. Study of the unusual metabolism of the EGF receptor in the MDA-MB-231 human breast cancer cell line will continue with emphasis on characterization EGF receptor containing endosomes from these cells. Phosphorylation of the EGF receptor will also be more thoroughly examined in these cells. Initial characterization of the c-erbB protein from Drosophila will be begun using antisera prepared against recombinant protein. Analysis of a M=100,000 Drosophila growth factor binding protein will continue. Structural comparison of the v-erbA and c-erbA proteins will be performed, again, using antiserum prepared against recombinant protein.