Analysis of Ligand Binding ErbB Receptor Tyrosine Kinases
Abstract
Growth factor-receptor tyrosine kinases (RTK's) play a central role in the coordination of cell growth, differentiation and other activities in multicellular organism. Molecular lesions in and/or aberrant expression of RTK' S can lead to cancer. There is a particularly strong correlation between the erbB2 (neu/HER-2) receptor and breast cancer. The cell-surface location of the erbB2 receptor makes it an obvious target for novel therapies. The purpose of this research is to gain insight into the structure of the extracellular domain of this receptor and its mode of activation in order to aid in the development of new antagonists. ErbB2 is one of a family of 4 RTK' S which also includes the epidermal growth factor receptor (EGFR). The first Step in the stimulation of a response by a growth factor is dimerization of the receptor upon binding of the cognate ligand. We have crystals of the EGF induced homodimer of the soluble extracellular domain of EGFR. Determination of this structure is in progress, and several derivatives have been identified. This structure will provide insight into the specific molecular events that drive erbB receptor dimerization.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2000
- Accession Number
- ADB265976
Entities
People
- Kathryn Ferguson
- Mark A. Lemmon
Organizations
- University of Pennsylvania