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Biotech / Medical : EntreMed (ENMD) -- Ignore unavailable to you. Want to Upgrade?

To: Jon Koplik who wrote (1852)	3/17/1999 11:17:00 PM
From: tnsaf	Respond to of 2135

I just noticed that the "Subscriber" field indicates the university I'm connecting from - must be from my IP address. Since the article is copyrighted, the abstract is below. Jason -------------------------------------------- Vol. 96, Issue 6, 2811-2816, March 16, 1999 Cell Biology Angiostatin binds ATP synthase on the surface of human endothelial cells Tammy L. Moser,, M. Sharon Stack, Iain Asplin, Jan J. Enghild, Peter Højrup§, Lorraine Everitt, Susan Hubchak¶, H. William Schnaper¶, and Salvatore V. Pizzo* * Department of Pathology, Duke University Medical Center, Durham, NC 27710; Departments of Obstetrics and Gynecology and ¶ Pediatrics, Northwestern University Medical School, Chicago, IL 60611; and § Department of Molecular Biology, Odense University, Denmark 5230 Communicated by M. Judah Folkman, Harvard Medical School, Brookline, MA, January 11, 1999 (received for review May 24, 1998) Angiostatin, a proteolytic fragment of plasminogen, is a potent antagonist of angiogenesis and an inhibitor of endothelial cell migration and proliferation. To determine whether the mechanism by which angiostatin inhibits endothelial cell migration and/or proliferation involves binding to cell surface plasminogen receptors, we isolated the binding proteins for plasminogen and angiostatin from human umbilical vein endothelial cells. Binding studies demonstrated that plasminogen and angiostatin bound in a concentration-dependent, saturable manner. Plasminogen binding was unaffected by a 100-fold molar excess of angiostatin, indicating the presence of a distinct angiostatin binding site. This finding was confirmed by ligand blot analysis of isolated human umbilical vein endothelial cell plasma membrane fractions, which demonstrated that plasminogen bound to a 44-kDa protein, whereas angiostatin bound to a 55-kDa species. Amino-terminal sequencing coupled with peptide mass fingerprinting and immunologic analyses identified the plasminogen binding protein as annexin II and the angiostatin binding protein as the /-subunits of ATP synthase. The presence of this protein on the cell surface was confirmed by flow cytometry and immunofluorescence analysis. Angiostatin also bound to the recombinant -subunit of human ATP synthase, and this binding was not inhibited by a 2,500-fold molar excess of plasminogen. Angiostatin's antiproliferative effect on endothelial cells was inhibited by as much as 90% in the presence of anti--subunit ATP synthase antibody. Binding of angiostatin to the /-subunits of ATP synthase on the cell surface may mediate its antiangiogenic effects and the down-regulation of endothelial cell proliferation and migration.