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

J. Biol. Chem., Vol. 282, Issue 8, 5749-5760, February 23, 2007

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 282/8/5749    most recent M610903200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted 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 Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Chen, C.-J. Articles by Shively, J. E. Search for Related Content PubMed PubMed Citation Articles by Chen, C.-J. Articles by Shively, J. E. Social Bookmarking                      What's this?

Mutation Analysis of the Short Cytoplasmic Domain of the Cell-Cell Adhesion Molecule CEACAM1 Identifies Residues That Orchestrate Actin Binding and Lumen Formation^*

Charng-Jui Chen¹, Julia Kirshner¹², Mark A. Sherman, Weidong Hu, Tung Nguyen, and John E. Shively³

From the Divisions of Immunology and Information Sciences, Beckman Research Institute of the City of Hope, Duarte, California 91010

CEACAM1-4S (carcinoembryonic antigen cell adhesion molecule 1, with 4 ectodomains and a short, 12-14 amino acid cytoplasmic domain) mediates lumen formation via an apoptotic and cytoskeletal reorganization mechanism when mammary epithelial cells are grown in a three-dimensional model of mammary morphogenesis. We show by quantitative yeast two-hybrid, BIAcore, NMR HSQC and STD, and confocal analyses that amino acids phenylalanine (Phe⁴⁵⁴) and lysine (Lys⁴⁵⁶) are key residues that interact with actin orchestrating the cytoskeletal reorganization. A CEACAM1 membrane model based on vitamin D-binding protein that predicts an interaction of Phe⁴⁵⁴ at subdomain 3 of actin was supported by inhibition of binding of actin to vitamin D-binding protein by the cytoplasmic domain peptide. We also show that residues Thr⁴⁵⁷ and/or Ser⁴⁵⁹ are phosphorylated in CEACAM1-transfected cells grown in three-dimensional culture and that mutation analysis of these residues (T457A/S459A) or F454A blocks lumen formation. These studies demonstrate that a short cytoplasmic domain membrane receptor can directly mediate substantial intracellular signaling.

Received for publication, November 27, 2006 , and in revised form, December 21, 2006.

^* This work was supported by National Institutes of Health NCI Grant CA84202. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Table S1.

¹ Both authors contributed equally to this research.

² Current address: Dept. of Experimental Oncology, Cross Cancer Institute, University of Alberta, Edmonton, Canada.

³ To whom correspondence should be addressed: 1450 E. Duarte Rd., Duarte, CA 91010. Tel.: 626-359-8111 (ext. 62601); Fax: 626-301-8186; E-mail: jshively{at}coh.org.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				E. Klaile, M. M. Muller, C. Kannicht, W. Otto, B. B. Singer, W. Reutter, B. Obrink, and L. Lucka The Cell Adhesion Receptor Carcinoembryonic Antigen-related Cell Adhesion Molecule 1 Regulates Nucleocytoplasmic Trafficking of DNA Polymerase {delta}-Interacting Protein 38 J. Biol. Chem., September 7, 2007; 282(36): 26629 - 26640. [Abstract] [Full Text] [PDF]