HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 275, Issue 35, 26935-26943, September 1, 2000

This Article Full Text Full Text (PDF) All Versions of this Article: 275/35/26935    most recent M909242199v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Taheri, M. Articles by Stanners, C. P. Search for Related Content PubMed PubMed Citation Articles by Taheri, M. Articles by Stanners, C. P. Social Bookmarking                      What's this?

Self Recognition in the Ig Superfamily
IDENTIFICATION OF PRECISE SUBDOMAINS IN CARCINOEMBRYONIC ANTIGEN REQUIRED FOR INTERCELLULAR ADHESION^*

Maryam Taheri^§, Uri Saragovi^¶, Abraham Fuks, Joe Makkerh, John Mort, and Clifford P. Stanners^§**

From the  McGill Cancer Centre and the Departments of ^§ Biochemistry and ^¶ Pharmacology & Therapeutics, McGill University, 3655 Promenade Sir-William-Osler, Montréal, Québec H3G 1Y6, Canada and the  Shriners Hospital for Children, 1529 Cedar Ave., Montréal, Québec H3G 1A6, Canada

The homophilic binding of extracellular domains of membrane-bound immunoglobulin superfamily (IgSF) molecules is often required for intercellular adhesion and signaling. Carcinoembryonic antigen (CEA), a member of the IgSF, is a widely used tumor marker that functions in vitro as a homotypic intercellular adhesion molecule. CEA has also been shown to contribute to tumorigenicity by inhibiting cellular differentiation, an effect that requires the homophilic binding of its extracellular domains. It was of interest, therefore, to identify small subdomain sequences in CEA that could serve as a focus in the design of peptides that disrupt CEA-mediated intercellular adhesion. Three subdomains in the N-terminal domain of CEA, identified by site-directed deletions and point mutations, were shown to be required for intercellular adhesion. Cyclized peptides representing two of these subdomains, ⁴²NRQII and ⁸⁰QNDTG, were found to be effective in blocking CEA-mediated cellular aggregation when added to CEA-expressing transfectants in suspension. Intermolecular binding involving each of these subdomains is therefore essential for intercellular adhesion and cannot be compensated for by known binding contributions of other regions in the CEA molecule. In further support of this assumption, the binding epitope of an anti-CEA monoclonal antibody (monoclonal antibody A20) known to block CEA-mediated adhesion, was shown to bridge two of the three required subdomains: ⁴²NRQII and ³⁰GYSWYK.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				N. Korotkova, E. Cota, Y. Lebedin, S. Monpouet, J. Guignot, A. L. Servin, S. Matthews, and S. L. Moseley A Subfamily of Dr Adhesins of Escherichia coli Bind Independently to Decay-accelerating Factor and the N-domain of Carcinoembryonic Antigen J. Biol. Chem., September 29, 2006; 281(39): 29120 - 29130. [Abstract] [Full Text] [PDF]

				R. D. Blumenthal, H. J. Hansen, and D. M. Goldenberg Inhibition of Adhesion, Invasion, and Metastasis by Antibodies Targeting CEACAM6 (NCA-90) and CEACAM5 (Carcinoembryonic Antigen) Cancer Res., October 1, 2005; 65(19): 8809 - 8817. [Abstract] [Full Text] [PDF]

				G. Markel, R. Gruda, H. Achdout, G. Katz, M. Nechama, R. S. Blumberg, R. Kammerer, W. Zimmermann, and O. Mandelboim The Critical Role of Residues 43R and 44Q of Carcinoembryonic Antigen Cell Adhesion Molecules-1 in the Protection from Killing by Human NK Cells J. Immunol., September 15, 2004; 173(6): 3732 - 3739. [Abstract] [Full Text] [PDF]

				M. M. Comegys, S.-H. Lin, D. Rand, D. Britt, D. Flanagan, H. Callanan, K. Brilliant, and D. C. Hixson Two Variable Regions in Carcinoembryonic Antigen-related Cell Adhesion Molecule1 N-terminal Domains Located in or Next to Monoclonal Antibody and Adhesion Epitopes Show Evidence of Recombination in Rat but Not in Human J. Biol. Chem., August 13, 2004; 279(33): 35063 - 35078. [Abstract] [Full Text] [PDF]

				M. Taheri, H. U. Saragovi, and C. P. Stanners The Adhesion and Differentiation-inhibitory Activities of the Immunoglobulin Superfamily Member, Carcinoembryonic Antigen, Can Be Independently Blocked J. Biol. Chem., April 18, 2003; 278(17): 14632 - 14639. [Abstract] [Full Text] [PDF]

				N. L. Berinstein Carcinoembryonic Antigen as a Target for Therapeutic Anticancer Vaccines: A Review J. Clin. Oncol., April 15, 2002; 20(8): 2197 - 2207. [Abstract] [Full Text] [PDF]

				M. Kuroki, H. Abe, T. Imakiirei, S. Liao, H. Uchida, Y. Yamauchi, S. Oikawa, and M. Kuroki Identification and comparison of residues critical for cell-adhesion activities of two neutrophil CD66 antigens, CEACAM6 and CEACAM8 J. Leukoc. Biol., October 1, 2001; 70(4): 543 - 550. [Abstract] [Full Text] [PDF]

				E. Soeth, T. Wirth, H.-J. List, S. Kumbhani, A. Petersen, M. Neumaier, F. Czubayko, and H. Juhl Controlled Ribozyme Targeting Demonstrates an Antiapoptotic Effect of Carcinoembryonic Antigen in HT29 Colon Cancer Cells Clin. Cancer Res., July 1, 2001; 7(7): 2022 - 2030. [Abstract] [Full Text] [PDF]