BIOLOGY OF HHV8/KSHV G PROTEIN COUPLED RECEPTOR

HHV8/KSHV G 蛋白偶联受体的生物学

• 批准号: 2653230
• 负责人: MARVIN C GERSHENGORN
• 金额: $ 29.47万
• 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/2653230
• 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：该项目着重于HHV-8的G蛋白偶联受体 发现与卡波西的肉瘤有关。 最近有 已显示该受体通过磷酸肌醇 - 硫醇的功能 1,4,5-三磷酸 - 钙蛋白激酶C信号转导途径，至 诱导细胞增殖和转化；建议HHV-8/GPCR可能 在异常增殖中起必要的，即使没有足够的作用 由KS细胞或淋巴样B细胞展示。 目标的目标 研究是了解HHV-8 GPCR的生物学及其在 Ks的发病机理。 提出了三个具体目标。 首先是 描述信号传导机制和潜在调节的模式 HHV-8 GPCR，以及HHV-8 GPCR表达的生物学后果 各种细胞类型，例如COS，293T，NIH 3T3，上皮和B细胞。 这 第二是发现基于HHV-8 GPCR的高亲和力，特定的配体 类似于已知的趋化因子。 第三是确定 HHV-8 GPCR疾病发病机理。