The role of post-translational modifications of the CXCR4 amino terminus in stromal-derived factor 1α association and HIV-1 entry
The role of post-translational modifications of the CXCR4 amino terminus in stromal-derived factor 1α association and HIV-1 entry
复制标题
DOI：
10.1074/jbc.m203361200
复制
发表时间：
2002-08-16
影响因子：
4.8
通讯作者：
Choe, H
中科院分区：
文献类型：
--
作者：
Farzan, M;Babcock, GJ;Choe, H
趋化因子受体CXCR4在发育、免疫功能和人类免疫缺陷病毒1型（HIV-1）进入中起关键作用。在这里，我们证明了，像cc趋化因子受体CCR5和CCR2b一样，CXCR4通过其氨基末端酪氨酸的硫酸化进行翻译后修饰。酪氨酸21上的硫酸盐基团对CXCR4结合其配体基质衍生因子la的能力有很大贡献。酪氨酸硫酸化在cxcr4依赖性HIV-1进入过程中的作用低于ccr5依赖性HIV-1进入过程。在一些细胞系中，CXCR4在丝氨酸18处被硫酸软骨素链有效修饰，但是HIV-1的进入和基质衍生因子la的结合都不受这种糖胺聚糖缺失的影响。这些数据证明了酪氨酸硫酸盐在cxc趋化因子受体家族中的功能作用，并强调了CCR5和CXCR4在HIV-1利用中的普遍差异。
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 la. 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 la 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.