BIOLOGY OF HHV8/KSHV G PROTEIN COUPLED RECEPTOR

HHV8/KSHV G 蛋白偶联受体的生物学

• 批准号: 6362633
• 负责人: Enrique A Mesri
• 金额: $ 34.21万
• 依托单位: WEILL MEDICAL COLL OF CORNELL UNIV
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-04-01 至 2003-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6362633
• 关键词: G protein; Kaposi's sarcoma; biological signal transduction; human herpesvirus 8; interleukin 8; molecular cloning; molecular pathology; peptide analog; receptor binding; receptor expression; synthetic peptide; tissue /cell culture; transfection; virus receptors

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.

描述：该项目重点关注 HHV-8 的 G 蛋白偶联受体 被发现与卡波西肉瘤有关。 最近有 已证明该受体通过磷酸肌醇-肌醇发挥作用 1,4,5-三磷酸钙蛋白激酶C信号转导通路 诱导细胞增殖和转化；表明 HHV-8/GPCR 可能 在异常增殖中发挥必要的（如果不是充分的）作用 由KS细胞或淋巴瘤B细胞表现出。 本次活动的目标 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。 第一个是 描述潜在调节的信号机制和模式 HHV-8 GPCR，以及 HHV-8 GPCR 表达的生物学后果 各种细胞类型，如 cos、293T、NIH 3T3、上皮细胞和 B 细胞。 这 其次是发现基于 HHV-8 GPCR 的高亲和力、特异性配体 与已知的趋化因子类比。 三是确定角色 HHV-8 GPCR 在疾病发病机制中的作用。