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 investigate the basic mechanisms behind vascular development with the goal of discovering novel proteins involved in angiogenic processes. VEGF (Vascular Endothelial Growth Factor) is a growth factor that has been proven to promote angiogenesis in solid tumors. We undertook two screens: the first to identify the genes transcriptionally regulated by VEGF stimulation of endothelial cells, and the second to identify proteins which participate in the signal transduction pathways downstream of VEGF receptors. Our work focused on SOCS2 (Suppressor of Cytokine Signaling, an SH2-containing cytoplasmic protein. SOCS2 was pulled out of yeast two-hybrid screen for proteins that interact with VEGFR1. SOCS2 was present in the endothelium and associated specifically with stimulated VEGF receptors in a GST-pulldown system, suggesting a role in the regulation of angiogenesis. This project both informs the understanding of angiogenesis and has the potential benefit of identifying a novel, specific target for anti-angiogenic therapy.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2001
- Accession Number
- ADB268117
Entities
People
- Adrianne Wong
- Kevin Peters
Organizations
- Duke University Hospital