Functional Analysis of ERBB3 in the Mammary Gland
Abstract
The mammalian ErbB signaling network, composed of multiple polypeptide ligands belonging to the epidermal growth factor (EGF) superfamily, and four related type I receptor tyrosine kinases, EGFR/Erbpl-Erbp4, transduces both growth and differentiation signals in a variety of cell types. We have previously derived mice lacking EGF family growth factors, individually and in combination, to reveal roles in the mammary gland and gut. To investigate physiological roles for heparin-binding EGF (HB-EGF) we generated HB-EGF mice by targeted mutation of the gene. Although no defects in mammary gland development or function were found, we did discover defects in the architecture of the lung and heart valves suggesting HB-EGF normally mediates cellular differentiation in these tissues. We also found the same heart valve defect in mice with a targeted mutation of the ADAM-family integral membrane metalloprotease, Tumor Necrosis Factor-Alpha Converting enzyme (TACE) and mice lacking EGFR, suggesting that soluble HB-EGF is the critical EGFR-binding ligand regulating lung and cardiac valve maturation. Additionally, it appears that HB-EGF/EGFP signaling may modulate bone morphogenic protein signaling in heart valves.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2003
- Accession Number
- ADA417293
Entities
People
- David Lee
- Leslie F. Jackson
Organizations
- University of North Carolina at Chapel Hill