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

J. Biol. Chem., Vol. 282, Issue 37, 27343-27353, September 14, 2007

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 282/37/27343    most recent M704096200v1 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 Davies, J. Q. Articles by Lin, H.-H. Search for Related Content PubMed PubMed Citation Articles by Davies, J. Q. Articles by Lin, H.-H. Social Bookmarking                      What's this?

The Role of Receptor Oligomerization in Modulating the Expression and Function of Leukocyte Adhesion-G Protein-coupled Receptors^*

John Q. Davies¹, Gin-Wen Chang¹, Simon Yona, Siamon Gordon, Martin Stacey², and Hsi-Hsien Lin³

From the Sir William Dunn School of Pathology, University of Oxford, South Parks Rd., Oxford, OX1 3RE, United Kingdom and the Department of Microbiology and Immunology, College of Medicine, Chang Gung University, 259 Wen-Hwa 1st Rd., Kwei-San, Tao-Yuan, Taiwan

The human leukocyte adhesion-G protein-coupled receptors (GPCRs), the epidermal growth factor (EGF)-TM7 proteins, are shown here to function as homo- and hetero-oligomers. Using cell surface cross-linking, co-immunoprecipitation, and fluorescence resonance energy transfer analysis of EMR2, an EGF-TM7 receptor predominantly expressed in myeloid cells, we demonstrate that it forms dimers in a reaction mediated exclusively by the TM7 moiety. We have also identified a naturally occurring but structurally unstable EMR2 splice variant that acts as a dominant negative modulator by dimerizing with the wild type receptor and down-regulating its expression. Additionally, heterodimerization between closely related EGF-TM7 members is shown to result in the modulation of expression and ligand binding properties of the receptors. These findings suggest that receptor homo- and hetero-oligomerization play a regulatory role in modulating the expression and function of leukocyte adhesion-GPCRs.

Received for publication, May 17, 2007 , and in revised form, July 9, 2007.

^* This study was supported by research grants from the Nuffield Oxford Medical Fellowship (to J. Q. D.), grants from the British Heart Foundation and the Medical Research Council (both to S. G.), Chang Gung Memorial Hospital Grants CMRPD33008 and CMRPD140131 (to H-H. L.), and National Science Council-Taiwan Grant NSC95-2320-B-182-012 (to H-H. L.). 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 Figs. S1-S4.

¹ These authors contributed equally to this work.

² To whom correspondence may be addressed. E-mail: martin.stacey{at}path.ox.ac.uk.

³ To whom correspondence may be addressed. E-mail: hhlin{at}mail.cgu.edu.tw.

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

This article has been cited by other articles:

				J.-P. Silva, V. Lelianova, C. Hopkins, K. E. Volynski, and Y. Ushkaryov Functional Cross-interaction of the Fragments Produced by the Cleavage of Distinct Adhesion G-protein-coupled Receptors J. Biol. Chem., March 6, 2009; 284(10): 6495 - 6506. [Abstract] [Full Text] [PDF]

				H. Veninga, S. Becker, R. M. Hoek, M. Wobus, E. Wandel, J. van der Kaa, M. van der Valk, A. F. de Vos, H. Haase, B. Owens, et al. Analysis of CD97 Expression and Manipulation: Antibody Treatment but Not Gene Targeting Curtails Granulocyte Migration J. Immunol., November 1, 2008; 181(9): 6574 - 6583. [Abstract] [Full Text] [PDF]