Functional Analysis of the ErbB4 Receptor Tyrosine Kinase.

摘要

My laboratory studies the signaling network comprised of the epidermal growth factor (EGF) family of peptide hormones and the ErbB family of receptor tyrosine kinases. We are particularly interested in elucidating the roles that these hormones and receptors play in breast cancer and in developing reagents that target these hormones and receptor and may be use in diagnosing or treating breast cancer. In part due to the generous support of this career development award, we have made progress on four fronts. (1) We have identified and characterized novel small-molecule EGFR antagonists. Some of these hold promise as breast tumor imaging agents specific for tumors that overexpress EGFR. (2) We have used a set of constitutively active ErbB4 mutants to determine that ErbB4 signaling inhibits the proliferation of non-malignant and malignant human mammary cell lines. This suggests that ErbB4 may be a mammary- specific tumor suppressor. (3) We have characterized four novel EGF family hormones. (4) Moreover, we have made mutants of two EGF family hormones that have enabled us to identify residues critical for activation of ErbB4 signaling by these hormones. These data may lead to synthetic, specific ErbB4 agonists and antagonists that could be used to define the role of ErbB4 in breast cancer or could be used to prevent breast cancer.