Angiomotin: an angiostatin binding protein that regulates endothelial cell migration and tube formation.

Abstract	Angiostatin, a circulating inhibitor of angiogenesis, was identified by its ability to maintain dormancy of established metastases in vivo. In vitro, angiostatin inhibits endothelial cell migration, proliferation, and tube formation, and induces apoptosis in a cell type-specific manner. We have used a construct encoding the kringle domains 1--4 of angiostatin to screen a placenta yeast two-hybrid cDNA library for angiostatin-binding peptides. Here we report the identification of angiomotin, a novel protein that mediates angiostatin inhibition of migration and tube formation of endothelial cells. In vivo, angiomotin is expressed in the endothelial cells of capillaries as well as larger vessels of the human placenta. Upon expression of angiomotin in HeLa cells, angiomotin bound and internalized fluorescein-labeled angiostatin. Transfected angiomotin as well as endogenous angiomotin protein were localized to the leading edge of migrating endothelial cells. Expression of angiomotin in endothelial cells resulted in increased cell migration, suggesting a stimulatory role of angiomotin in cell motility. However, treatment with angiostatin inhibited migration and tube formation in angiomotin-expressing cells but not in control cells. These findings indicate that angiostatin inhibits cell migration by interfering with angiomotin activity in endothelial cells.
Authors	B Troyanovsky, T Levchenko, G Månsson, O Matvijenko, L Holmgren
Journal	The Journal of cell biology (J Cell Biol) Vol. 152 Issue 6 Pg. 1247-54 (Mar 19 2001) ISSN: 0021-9525 [Print] United States
PMID	11257124 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	AMOT protein, human Angiomotins Carrier Proteins Intercellular Signaling Peptides and Proteins Membrane Proteins Microfilament Proteins Peptide Fragments Recombinant Fusion Proteins Angiostatins Plasminogen Protein-Tyrosine Kinases Focal Adhesion Kinase 1 Focal Adhesion Protein-Tyrosine Kinases PTK2 protein, human Ptk2 protein, mouse
Topics	Amino Acid Sequence Angiomotins Angiostatins Animals Blood Vessels (growth & development, physiology) Blotting, Northern Carrier Proteins (chemistry, genetics, metabolism) Cattle Cell Line Cell Movement (physiology) Cells, Cultured Endothelium, Vascular (cytology, drug effects, physiology) Focal Adhesion Kinase 1 Focal Adhesion Protein-Tyrosine Kinases Genes, Reporter Humans Intercellular Signaling Peptides and Proteins Kringles (genetics) Membrane Proteins Mice Microfilament Proteins Microscopy, Fluorescence Molecular Sequence Data Neovascularization, Physiologic (physiology) Peptide Fragments (metabolism) Plasminogen (metabolism) Protein Binding Protein-Tyrosine Kinases (metabolism) Pseudopodia (metabolism) Recombinant Fusion Proteins (metabolism) Transfection Two-Hybrid System Techniques

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.

Realize the full power of the drug-disease research graph!