G PROTEIN BETA GAMMA SIGNALING SYSTEMS IN VIVO

体内 G 蛋白 Beta GAMMA 信号系统

• 批准号: 2687632
• 负责人: JANET D ROBISHAW
• 金额: $ 22.1万
• 依托单位: PENNSYLVANIA STATE UNIV HERSHEY MED CTR
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-01 至 2002-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2687632
• 关键词: G protein; affinity chromatography; beta adrenergic receptor; biological signal transduction; dimer; gene expression; heart cell; mutant; protein structure function; ribozymes; tissue /cell culture; transfection; western blottings

DESCRIPTION (Investigator's Abstract); In most cases, it is not known which receptors activate which G proteins to modulate which effectors in vivo. Reconstitution approaches have begun to provide invaluable information on the potential of specific G protein alpha or beta-gamma subunits to interact with particular receptors or effectors in vitro. Nevertheless, it is clear that there is a far wider range of potential interactions that occur in reconstituted systems than actually do occur in native membrane or cellular systems. This is exemplified by the finding that beta-adrenergic receptor activates both Gs and Gi equally in a reconstituted system, whereas this receptor activates Gs exclusively in an intact cardiac cell system. From these and other studies, it has become increasingly clear that although a receptor can activate several types of G proteins in vitro, the signaling pathways that the receptor regulates in vivo is much more restricted. This suggests that homology among signaling components and/or the artificial assay systems that have been employed in vitro do not provide the conditions necessary to distinguish what may be subtle, but important, mechanistic differences among signaling components that operate in vivo. There is increasing evidence that these mechanistic differences reflect not only biochemical, but also spatial differences, among signaling components. Hence, ascribing functional roles for G protein alpha and beta-gamma subunits in vivo remains a critical and formidable task. The focus of this application is on the development and application of new approaches to allow the role of the specific beta-gamma dimer in a particular receptor-effector pathway to be determined in vivo. Multiple approaches, including reverse genetics, biochemical, and immunological strategies, will be taken. Validation of results with all of these approaches will provide strong support for the role of a specific beta-gamma dimer in a particular receptor signaling pathway.

描述（研究者摘要）；在大多数情况下，不知道是哪一种