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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
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
Ilan ,
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/ -catenin association functions to
regulate -catenin localization and, moreover, to modulate
-catenin tyrosine phosphorylation levels. Here we show that: 1) not
only -catenin, but also -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 -catenin association; 4) PECAM-1 recruits -catenin to cell-cell junctions in
transfected SW480 cells; and 5) -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.
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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Copyright © 2000 by the American Society for Biochemistry and Molecular Biology.
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