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

J. Biol. Chem., Vol. 280, Issue 30, 27866-27871, July 29, 2005

This Article Full Text Full Text (PDF) All Versions of this Article: 280/30/27866    most recent M503770200v1 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 Pushkarsky, T. Articles by Bukrinsky, M. I. Search for Related Content PubMed PubMed Citation Articles by Pushkarsky, T. Articles by Bukrinsky, M. I. Social Bookmarking                      What's this?

Cell Surface Expression of CD147/EMMPRIN Is Regulated by Cyclophilin 60^*

Tatiana Pushkarsky, Vyacheslav Yurchenko, Christophe Vanpouille, Beda Brichacek, Iosif Vaisman¶, Shigetsugu Hatakeyama||, Keiichi I. Nakayama||, Barbara Sherry**, and Michael I. Bukrinsky

From the The George Washington University Medical Center, Washington, D. C. 20037, the Albert Einstein College of Medicine of Yeshiva University, Bronx, New York 10461, the ^¶George Mason University, Fairfax, Virginia 22030, the ^||Medical Institute of Bioregulation, Kyushu University, Fukuoka-shi 812-8582, Japan, and the ^**North Shore Long Island Jewish Research Institute, Manhasset, New York 11030

CD147, also known as extracellular matrix metalloproteinase inducer, is a regulator of matrix metalloproteinase production and also serves as a signaling receptor for extracellular cyclophilins. Previously, we demonstrated that cell surface expression of CD147 is sensitive to cyclophilin-binding drug cyclosporin A, suggesting involvement of a cyclophilin in the regulation of intracellular transport of CD147. In this report, we identify this cyclophilin as cyclophilin 60 (Cyp60), a distinct member of the cyclophilin family of proteins. CD147 co-immunoprecipitated with Cyp60, and confocal immunofluorescent microscopy revealed intracellular co-localization of Cyp60 and CD147. This interaction with Cyp60 involved proline 211 of CD147, which was shown previously to be critical for interaction between CD147 and another cyclophilin, cyclophilin A, in solution. Mutation of this proline residue abrogated co-immunoprecipitation of CD147 and Cyp60 and reduced surface expression of CD147 on the plasma membrane. Suppression of Cyp60 expression using RNA interference had an effect similar to that of cyclosporin A: reduction of cell surface expression of CD147. These results suggest that Cyp60 plays an important role in the translocation of CD147 to the cell surface. Therefore, Cyp60 may present a novel target for therapeutic interventions in diseases where CD147 functions as a pathogenic factor, such as cancer, human immunodeficiency virus infection, or rheumatoid arthritis.

Received for publication, April 7, 2005 , and in revised form, April 29, 2005.

^* This work was supported in part by National Institutes of Health Grants R03 A1057018 and R21 A1060720 (to M. I. B.) and R01 AI029110 (to B. S.) and by funds from George Washington University. 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.

To whom correspondence should be addressed: GWU Medical Center, Ross Hall Rm. 734, 2300 Eye St. N. W., Washington, D. C. 20037. Tel.: 202-994-2036; Fax: 202-994-2913; E-mail: mtmmib{at}gwumc.edu.

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

This article has been cited by other articles:

				Y. Yang, N. Lu, J. Zhou, Z.-n. Chen, and P. Zhu Cyclophilin A up-regulates MMP-9 expression and adhesion of monocytes/macrophages via CD147 signalling pathway in rheumatoid arthritis Rheumatology, September 1, 2008; 47(9): 1299 - 1310. [Abstract] [Full Text] [PDF]

				X.-L. Yu, T. Hu, J.-M. Du, J.-P. Ding, X.-M. Yang, J. Zhang, B. Yang, X. Shen, Z. Zhang, W.-D. Zhong, et al. Crystal Structure of HAb18G/CD147: IMPLICATIONS FOR IMMUNOGLOBULIN SUPERFAMILY HOMOPHILIC ADHESION J. Biol. Chem., June 27, 2008; 283(26): 18056 - 18065. [Abstract] [Full Text] [PDF]

				S. M. Gallagher, J. J. Castorino, D. Wang, and N. J. Philp Monocarboxylate Transporter 4 Regulates Maturation and Trafficking of CD147 to the Plasma Membrane in the Metastatic Breast Cancer Cell Line MDA-MB-231 Cancer Res., May 1, 2007; 67(9): 4182 - 4189. [Abstract] [Full Text] [PDF]