TYROSINE SULFATION OF CHEMOKINE RECEPTORS

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。CCR 5趋化因子受体是已知的HIV 1进入的辅助受体。在CCR 5的细胞外N-末端区段处的酪氨酸的硫酸化已显示介导病毒外壳蛋白gp 120的结合。我们最近阐明了对应于CCR 5的N-末端的肽的酪氨酸硫酸化的模式和时间序列（Seibert C，Cadene M，Sanfiz A，Chait BT，Sakmar TP，Tyrosine sulfation of CCR 5 N-terminal peptide by tyrosylprotein sulfotransferases 1 and 2 follows a discrete pattern and temporal sequence.美国国家科学院院刊。2002年8月20日;99（17）：11031-6.）到目前为止，对酪氨酸硫酸化在趋化因子受体功能中的作用或这种修饰的普遍性知之甚少。特别是，需要更多的工作来了解酪氨酸硫酸化如何影响受体结合其天然趋化因子配体的能力，并确定哪些受体对病毒感染至关重要。为了更好地理解这些方面的趋化因子受体的功能，我们进行了表征的酪氨酸硫酸化全长CCR 5以及其他趋化因子受体。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. CCR5 chemokine receptor is a known coreceptor of HIV1 entry. Sulfation of tyrosines at the extracellular N-terminal segment of CCR5 has been shown to mediate binding of the viral coat protein gp120. We recently elucidated the pattern and temporal sequence of tyrosine sulfation of a peptide corresponding to the N-terminus of CCR5 (Seibert C, Cadene M, Sanfiz A, Chait BT, Sakmar TP, Tyrosine sulfation of CCR5 N-terminal peptide by tyrosylprotein sulfotransferases 1 and 2 follows a discrete pattern and temporal sequence. Proc Natl Acad Sci U S A. 2002 Aug 20;99(17):11031-6.) So far little is known about the role of tyrosine sulfation in chemokine receptors function, or the generality of this modification. In particular, more work is needed to understand how tyrosine sulfation affects the receptor's ability to bind its natural chemokine ligands and to determine in which receptors it is critical to viral infection. To better understand these aspects of chemokine receptors function, we have undertaken the characterization of tyrosine sulfation in full-length CCR5 as well as other chemokine receptors.