Accession Number : ADA337396

Title :   Role of the erbB3 Gene Product in Breast Cancer Cell Proliferation

Descriptive Note : Annual rept. 1 Sep 96-31 Aug 97

Corporate Author : IOWA UNIV IOWA CITY

Personal Author(s) : Koland, John G.

PDF Url : ADA337396

Report Date : SEP 1997

Pagination or Media Count : 17

Abstract : The role of the ErbB3 protein in breast cancer cell proliferation was examined. In the first year of funding, it was demonstrated that the ErbB3 protein, although possessing a protein tyrosine kinase (PTK) homology domain, is in fact devoid of intrinsic PTK activity. In the second year of funding, we demonstrated the critical dependence of heregulin signaling upon the PTK activity of the ErbB2 protein, and characterized the interaction of ErbB3 with phosphatidylinositol 3-kinase, an enzyme known to be involved in heregulin signaling. In the previous year, we have clarified the role of the Shc protein in the activation of the Ras/mitogen activated protein kinase (MAPK) pathway. By site directed mutagenesis, we demonstrated that tyrosine 1325 in the ErbB3 protein serves when phosphorylated as a docking site for Shc, and that this single residue is essential for the activation of the Ras/MAPK pathway. We also began an exhaustive examination of other tyrosine residues in the ErbB3 C-terminus. We generated a series of recombinant ErbB3 proteins in which C-terminal tyrosine residues are substituted with phenylalanine, so that the roles of these sites in the activation of mitogenic signaling via the phosphatidylinositol 3-kinase pathway can be elucidated.

Descriptors :   *CELL DIVISION, *BREAST CANCER, ENZYMES, PROTEINS, GENES, CELLS(BIOLOGY), GROWTH(PHYSIOLOGY).

Subject Categories : Anatomy and Physiology
      Medicine and Medical Research

Distribution Statement : APPROVED FOR PUBLIC RELEASE