Functional Significance of Transcriptional Regulation by VEGF Receptor Tyrosine Kinases
Abstract
Angiogenesis plays a fundamental role in solid tumor growth and metastasis. The vasculature is for the most part quiescent in the adult, so it follows that anti-angiogenic therapies are an attractive method of targeting tumorigenesis. Thus, the purpose of this study was to study the basic mechanisms behind vascular development with the goal of discovering novel proteins involved in angiogenic signal transduction pathways. This project both informs the understanding of angiogenesis and has the potential benefit of identifying novel, specific targets for anti-angiogenic therapy. Two families of endothelial receptor tyrosine kinases play an essential role in angiogenesis: VEGF and Tie. In order to find new members of this signaling pathway, we performed a yeast two-hybrid screen of a human fetal heart library using the VEGFR1 kinase domain as bait. We discovered that VEGFR1 associated with SOCS2 in a specific, kinase-dependent manner. SOCS2 is a member of the SOCS family of cytoplasmic signaling proteins that share homology in their C-terminal SOCS-box. Interestingly, other members of the family demonstrate a negative regulatory effect on cytokine signaling. Thus, we hypothesized that SOCS2 has a role on VEGF growth factor signaling through the VEGFR1 receptor.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2000
- Accession Number
- ADB266144
Entities
People
- Adrianne Wong
- Kevin Peters
Organizations
- Duke University Hospital