The Role of Post-translational Modifications of the CXCR4 Amino Terminus in Stromal-derived Factor 1α Association and HIV-1 Entry
2002; Elsevier BV; Volume: 277; Issue: 33 Linguagem: Inglês
10.1074/jbc.m203361200
ISSN1083-351X
AutoresMichael Farzan, Gregory J. Babcock, Natalya Vasilieva, Paulette L. Wright, Enko Kiprilov, Tajib A. Mirzabekov, Hyeryun Choe,
Tópico(s)Immunotherapy and Immune Responses
ResumoThe 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 1α. 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 1α 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.
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