BIOLOGY OF HHV8/KSHV G PROTEIN COUPLED RECEPTOR

项目描述：本项目主要研究HHV-8的G蛋白偶联受体 这与卡波西肉瘤有关。 它最近 已经证明这种受体通过磷酸肌醇-肌醇起作用 1，4，5-三磷酸-钙-蛋白激酶C信号转导途径， 诱导细胞增殖和转化;提示HHV-8/GPCR可能 在异常增殖中发挥必要的作用，如果不是足够的话。 由KS细胞或淋巴瘤性B细胞表现。 这一目标 研究的目的是了解HHV-8 GPCR的生物学，及其在 KS的发病机制。 提出了三个具体目标。 一是 描绘信号机制和模式的潜在调节 HHV-8 GPCR，以及HHV-8 GPCR表达在 各种细胞类型，如cos、293 T、NIH 3 T3、上皮细胞和B细胞。 的 第二是发现高亲和力的HHV-8特异性配体， 与已知趋化因子相似 第三是确定角色 HHV-8 GPCR在疾病发病机制中的作用。

DESCRIPTION: This project focuses on a G protein-coupled receptor of HHV-8 which was found to be associated with Kaposi's sarcoma. It has recently been shown that this receptor functions via the phosphoinositide-inositol 1,4,5-triphosphate-calcium-protein kinase C signal transduction pathway, to induce cell proliferation and transformation; suggesting that HHV-8/GPCR may play a necessary, if not sufficient role in the abnormal proliferation exhibited by KS cells or lymphomatous B cells. The objectives of this research are to understand the biology of HHV-8 GPCR, and its role in the pathogenesis of KS. Three specific aims are proposed. The first is to delineate the signaling mechanisms and modes of potential regulation of HHV-8 GPCR, and the biological consequences of HHV-8 GPCR expression in various cell types, such as cos, 293T, NIH 3T3, epithelial and B cells. The second is to discover high affinity, specific ligands for HHV-8 GPCR based on analogy to known chemokines. The third is to determine the roles of HHV-8 GPCR in disease pathogenesis.