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Originally published In Press as doi:10.1074/jbc.M001857200 on May 5, 2000

J. Biol. Chem., Vol. 275, Issue 28, 21435-21443, July 14, 2000
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Platelet-Endothelial Cell Adhesion Molecule-1 (CD31), a Scaffolding Molecule for Selected Catenin Family Members Whose Binding Is Mediated by Different Tyrosine and Serine/Threonine Phosphorylation*

Neta IlanDagger , Larry Cheung, Emese Pinter, and Joseph A. Madri§

From the Department of Pathology, Yale University School of Medicine, New Haven, Connecticut 06520

Platelet-endothelial cell adhesion molecule (PECAM)-1 is a 130-kDa glycoprotein commonly used as an endothelium-specific marker. Evidence to date suggests that PECAM-1 is more than just an endothelial cell marker but is intimately involved in signal transduction pathways. This is mediated in part by phosphorylation of specific tyrosine residues within the ITAM domain of PECAM-1 and by recruitment of adapter and signaling molecules. Recently we demonstrated that PECAM-1/beta -catenin association functions to regulate beta -catenin localization and, moreover, to modulate beta -catenin tyrosine phosphorylation levels. Here we show that: 1) not only beta -catenin, but also gamma -catenin is associated with PECAM-1 in vitro and in vivo; 2) PKC enzyme directly phosphorylates purified PECAM-1; 3) PKC-derived PECAM-1 serine/threonine phosphorylation inversely correlates with gamma -catenin association; 4) PECAM-1 recruits gamma -catenin to cell-cell junctions in transfected SW480 cells; and 5) gamma -catenin may recruit PECAM-1 into an insoluble cytoskeletal fraction. These data further support the concept that PECAM-1 functions as a binder and modulator of catenins and provides a molecular mechanism for previously reported PECAM-1/cytoskeleton interactions.


* This work was supported in part by U.S. Public Health Service Grants R37-HL28373 and PO1-DK38979 (to J. A. M.), a Charles H. Hood grant (to E. P.), and a Reed Foundation Fellowship (to N. I.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Dagger Current address: Insight Ltd., P. O. Box 2128, Rabin Science Park, Rehovat 76121, Israel.

§ To whom correspondence should be addressed: Dept. of Pathology, Yale University School of Medicine, 310 Cedar St., P.O. Box 208023, New Haven, CT 06520-8023. Tel.: 203-785-3763; Fax: 203-785-7303; E-mail: joseph.madri@yale.edu.


Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.
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