1. A short synthetic peptide inhibits signal transduction, migration and angiogenesis mediated by Tie2 receptor
- Author
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Anne Eichmann, Marie-Pierre Simon, Ferdinand le Noble, Roselyne Tournaire, Jacques Pouysségur, Patrick England, Institut de signalisation, biologie du développement et cancer (ISBDC), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), Université Côte d'Azur (UCA)-UNICANCER, Pathologie vasculaire et endocrinologie rénale - Chaire de médecine expérimentale (INSERM U36), Collège de France (CdF (institution))-Institut National de la Santé et de la Recherche Médicale (INSERM), Biophysique des macromolécules et de leurs interactions (Plate-forme), Institut Pasteur [Paris], Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), Biophysique des Macromolécules et de leurs Interactions, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), UNICANCER-Université Côte d'Azur (UCA), Université Nice Sophia Antipolis (1965 - 2019) (UNS), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), and Darcourt, Cecilia
- Subjects
Vascular Endothelial Growth Factor A ,MESH: Signal Transduction ,Umbilical Veins ,Angiogenesis ,Peptide ,Chick Embryo ,[SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC] ,[SDV.BC.IC] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB] ,Biochemistry ,0302 clinical medicine ,Cell Movement ,[SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB] ,MESH: Animals ,MESH: Endothelial Cells ,Enzyme Inhibitors ,MESH: Cell Movement ,Cells, Cultured ,chemistry.chemical_classification ,0303 health sciences ,biology ,Angiotensin II ,MESH: Chick Embryo ,Angiopoietin receptor ,Receptor, TIE-2 ,MESH: Receptor, TIE-2 ,Cell biology ,Vascular endothelial growth factor A ,surgical procedures, operative ,Angiopoietin-1 ,MESH: Enzyme Inhibitors ,030220 oncology & carcinogenesis ,MESH: Oligopeptides ,embryonic structures ,cardiovascular system ,Biological Assay ,MESH: Angiotensin II ,Signal transduction ,Oligopeptides ,tissues ,MESH: Neovascularization, Physiologic ,Signal Transduction ,MESH: Cells, Cultured ,Scientific Report ,Neovascularization, Physiologic ,MESH: Umbilical Veins ,MESH: Binding, Competitive ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,MESH: Biological Assay ,Binding, Competitive ,MESH: Mitogen-Activated Protein Kinase Kinases ,Angiopoietin ,03 medical and health sciences ,[SDV.CAN] Life Sciences [q-bio]/Cancer ,Peptide Library ,Consensus Sequence ,Genetics ,[SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology ,[SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC] ,Animals ,Humans ,[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology ,MESH: Consensus Sequence ,Peptide library ,Molecular Biology ,030304 developmental biology ,Mitogen-Activated Protein Kinase Kinases ,MESH: Humans ,MESH: Vascular Endothelial Growth Factor A ,Endothelial Cells ,chemistry ,MESH: Angiotensin I ,biology.protein ,MESH: Peptide Library ,sense organs ,Angiotensin I - Abstract
International audience; 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.
- Published
- 2004