Heregulin-Induced Growth Factor Receptor Signaling and Breast Carcinogenesis.
Abstract
We are studying how the signaling network composed of the Epidermal Growth Factor (EGF) family of peptide hormones and the ErbB family of receptor tyrosine kinases is differentially activated and coupled to physiologic responses. Because deregulation of this signaling network plays a significant role in the genesis or progression of several different human metastatic diseases, an understanding of the basic 'wiring' of this network is required to elucidate the mechanisms of these diseases. We have generated a panel of cell lines based on the Interleukin-3 (IL3) -dependent Ba/F3 mouse hematopoietic cell line that ectopically express the four ErbB family receptors. We have then identified the patterns of ErbB family receptor phosphorylation and IL3-independent responses stimulated by different EGF family hormones. We will present data supporting several concepts that have emerged from these studies: (1) Differential Activation by EGF Family Hormones. EGF family hormones can be assigned to three distinct functional groups based on their stimulation of ErbB family receptor phosphorylation. (2) Differential Coupling by ErbB Family Receptors. ErbB family receptors and combinations of receptors differentially couple to IL3-independent responses in Ba/F3 cells. Furthermore, ErbB family receptors directly activated by ligand binding behave differently from receptors activated in trans through receptor heterodimerization.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 1997
- Accession Number
- ADA331278
Entities
People
- David F. Stern
- David J. Riese
Organizations
- Yale University