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Originally published In Press as doi:10.1074/jbc.M203361200 on May 28, 2002

J. Biol. Chem., Vol. 277, Issue 33, 29484-29489, August 16, 2002
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The Role of Post-translational Modifications of the CXCR4 Amino Terminus in Stromal-derived Factor 1alpha Association and HIV-1 Entry*

Michael FarzanDagger , Gregory J. BabcockDagger , Natalya Vasilieva§, Paulette L. WrightDagger , Enko KiprilovDagger , Tajib MirzabekovDagger , and Hyeryun Choe§

From the Dagger  Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Department of Pathology, Division of AIDS, Harvard Medical School, Boston, Massachusetts 02115 and § Perlmutter Laboratory, Children's Hospital, Department of Pediatrics, Harvard Medical School, Boston, Massachusetts 02115

The chemokine receptor CXCR4 plays critical roles in development, immune function, and human immunodeficiency virus type 1 (HIV-1) entry. Here we demonstrate that, like the CC-chemokine receptors CCR5 and CCR2b, CXCR4 is posttranslationally modified by sulfation of its amino-terminal tyrosines. The sulfate group at tyrosine 21 contributes substantially to the ability of CXCR4 to bind its ligand, stromal derived factor 1alpha . Tyrosine sulfation plays a less significant role in CXCR4-dependent HIV-1 entry than in CCR5-dependent HIV-1 entry. In some cell lines, CXCR4 is efficiently modified by a chondroitin sulfate chain at serine 18, but neither HIV-1 entry nor stromal derived factor 1alpha binding was affected by loss of this glycosaminoglycan. These data demonstrate a functional role for tyrosine sulfate in the CXC-chemokine receptor family and underscore a general difference in HIV-1 utilization of CCR5 and CXCR4.


* This work was supported by National Institutes of Health Grants AI48425 (to M. F.) and AI43891 (to H. C.).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.

To whom correspondence should be addressed: Perlmutter Laboratory, 300 Longwood Ave., Children's Hospital, Boston, MA 02115. E-mail: hchoe@mbcrr.harvard.edu.


Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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