SIGNAL TRANSDUCTION OF THE D2 DOPAMINE RECEPTOR SUBTYPES

D2 多巴胺受体亚型的信号转导

• 批准号: 3478122
• 负责人: Susan Elizabeth Senogles
• 金额: $ 9.33万
• 依托单位: UNIVERSITY OF TENNESSEE HEALTH SCI CTR
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-04-01 至 1996-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3478122
• 关键词: G protein; SDS polyacrylamide gel electrophoresis; adenylate cyclase; biological signal transduction; calcium channel; cell membrane; clone cells; dopamine receptor; guanosine triphosphate; inositol phosphates; lipid metabolism; nucleic acid sequence; pertussis toxin; phosphatidylinositols; potassium channel; protein engineering; protein structure function; receptor binding; receptor coupling; site directed mutagenesis; thyrotropin releasing hormone; tissue /cell culture; transfection; vasoactive intestinal peptide; western blottings

The goal of this research proposal is to elucidate mechanisms which maintain the fidelity of transmembrane signal transduction. For the G protein coupled receptors, this process is made complex by the multiplicity of Gi subtypes. This proposal will focus on 1) construction and characterization of the Gi proteins which contain a substitution at the pertussis toxin modification site which will render them insensitive to pertussis toxin 2) creation of a cell which contains a single form of functional G protein 3) comparison of the G protein and effector coupling of the two splice forms of the rat striatal D2 dopamine receptor. These approaches will help to determine mechanisms which govern receptor signalling to effector systems. To date, little is known about the mechanisms which allow the high fidelity of transmembrane signal transduction in response to receptor activation. Using molecular biology techniques, G proteins which contain a mutation a the pertussis toxin site will ultimately be introduced into a permanent I clonal cell line, which after intoxication with pertussis toxin, will contain only the mutant G protein in a functional form. This approach will allow the receptor mediated effector responses to be examined in the presence of a single defined Gi subtype. These combined approaches will help to clarify the biochemical basis of signal transduction. Since dopamine is an important hormone in the periphery and a neurotransmitter in the CNS, understanding of its mechanisms of signalling could have important implications in some of the disorders thought to have a basis in i dopaminergic dysfunction, such as schizophrenia and Parkinson's disease.

本研究计划的目的是阐明其机制