A short synthetic peptide inhibits signal transduction, migration and angiogenesis mediated by Tie2 receptor

Item Type:	Article
Title:	A short synthetic peptide inhibits signal transduction, migration and angiogenesis mediated by Tie2 receptor
Creators Name:	Tournaire, R. and Simon, M.P. and le Noble, F. and Eichmann, A. and England, P. and Pouyssegur, J.
Abstract:	Tie2, an endothelial cell-specific receptor kinase, has an important role in tumour angiogenesis. In an attempt to identify peptides that specifically interact with and block the Tie2 pathway, a phage-displayed peptide library was screened on a recombinant Tie2 receptor. One peptide, NLLMAAS, completely abolished the binding to Tie2 of both angiopoietin 2 and angiopoietin 1 (Ang1). We further show that NLLMAAS specifically suppresses both Ang1-induced ERK activity and migration in human umbilical endothelial cells. Moreover, in vivo, this peptide inhibits angiogenesis in the chick chorioallantoic membrane assay. NLLMAAS is the first peptide described to interact with Tie2. Our results demonstrate that it is an efficient and specific antagonist of the binding of Tie2 ligands, and suggest that this peptide or its derivates may have potential applications in the treatment of angiogenesis diseases. It also represents a potent tool to dissect the molecular mechanisms involved in the Tie2 pathway.
Keywords:	Angiotensin I, Angiotensin II, Competitive Binding, Biological Assay, Cell Movement, Cultured Cells, Chick Embryo, Consensus Sequence, Endothelial Cells, Enzyme Inhibitors, Mitogen-Activated Protein Kinase Kinases, Physiologic Neovascularization, Oligopeptides, Peptide Library, TIE-2 Receptor, Signal Transduction, Umbilical Veins, Vascular Endothelial Growth Factor A, Animals, Chickens
Source:	EMBO Reports
ISSN:	1469-221X
Publisher:	Nature Publishing Group
Volume:	5
Number:	3
Page Range:	262-267
Date:	March 2004
Official Publication:	https://doi.org/10.1038/sj.embor.7400100
PubMed:	View item in PubMed

Repository Staff Only: item control page