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