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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2008;28:1640.)
© 2008 American Heart Association, Inc.

Cell Biology/Signaling

ECSM2, An Endothelial Specific Filamin A Binding Protein That Mediates Chemotaxis

Laura-Jane Armstrong; Victoria L. Heath; Sharon Sanderson; Sukhbir Kaur; James F.J. Beesley; John M.J. Herbert; John A. Legg; Richard Poulsom; Roy Bicknell

From the Angiogenesis Laboratory (L.-J.A., S.S., J.M.J.H., R.B.), Cancer Research UK, Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford; Cancer Research UK Angiogenesis Group (V.L.H., S.K., J.F.J.B., J.M.J.H., J.A.L., R.B.), The Institute for Biomedical Research, University of Birmingham Medical School, Edgbaston; and Cancer Research UK (R.P.), The London Research Institute, Lincoln’s Inn Fields, London, UK.

Correspondence to Roy Bicknell, Cancer Research UK Angiogenesis Group, The Institute for Biomedical Research, University of Birmingham Medical School, Edgbaston, Birmingham, B15 2TT, United Kingdom. E-mail R.Bicknell{at}bham.ac.uk

Objective— We aimed to characterize the expression and function of a novel transcript that bioinformatics analysis predicted to be endothelial specific, called endothelial-specific molecule-2 (ECSM2).

Methods and Results— A full-length cDNA was isolated and predicted ECSM2 to be a putative 205–amino acid transmembrane protein that bears no homology to any known protein. Quantitative polymerase chain reaction analysis in vitro and in situ hybridization analysis in vivo confirmed ECSM2 expression to be exclusively endothelial, and localization to the plasma membrane was shown. Knockdown of ECSM2 expression in human umbilical vein endothelial cells using siRNA resulted in both reduced chemotaxis and impaired tube formation on matrigel, a solubilized basement membrane, both processes involved in angiogenesis. A yeast 2 hybrid analysis using the ECSM2 intracellular domain identified filamin A as an interacting protein. This interaction was confirmed by precipitation of filamin-A from endothelial cell lysates by a GST-tagged intracellular domain of ECSM2.

Conclusion— This study is the first to characterize a novel cell surface protein ECSM2 that regulates endothelial chemotaxis and tube formation, and interacts with filamin A. These studies implicate a role for ECSM2 in angiogenesis via modulation of the actin cytoskeleton.

Expression of a novel endothelial specific gene called ECSM2 has been characterized in vitro and in vivo. ECSM2 is a transmembrane protein with no homology to known proteins that regulates endothelial tube formation and chemotaxis in vitro, and couples to filamin-A.

Key Words: endothelial genes • transmembrane proteins • filamin • cell signaling • chemotaxis • angiogenesis