MECHANISMS OF BETA2-ADRENOCEPTOR DOWNREGULATION

β2-肾上腺素受体下调的机制

• 批准号: 2713927
• 负责人: Robert H Moore
• 金额: $ 8.53万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-06-10 至 2001-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2713927
• 关键词: G protein; adenylate cyclase; alleles; beta adrenergic agent; beta adrenergic receptor; beta adrenergic receptor kinase; beta antiadrenergic agent; confocal scanning microscopy; electron microscopy; enzyme activity; genetic regulation; guanosinetriphosphatases; immunocytochemistry; immunoprecipitation; laboratory rabbit; lysosomes; phosphorylation; protein degradation; protein kinase A; protein kinase C; receptor coupling; receptor expression; receptor sensitivity; second messengers; tissue /cell culture; vaccinia virus

DESCRIPTION (Adapted from the applicant's abstract) The chronic use of beta2-adrenergic agonists may be associated with deterioration of asthma control and an increase in nonspecific bronchial responsiveness. This worsening in clinical status may be related to receptor densitization after prolonged exposure to agonist. The beta2-adrenoceptor (beta2-AR) couples to its effector, adenylyl cyclase, via a signal tranducing Gs protein. With agonist binding, there is rapid uncoupling of receptor from its Gs protein due to receptor phosphorylation. Within minutes, there is loss of membrane receptors due to endocytosis into early endosomes. With prolonged exposure to agonist, there is a loss of total cellular receptor. The candidate has completed a fellowship in pediatric pulmonology and is currently on the faculty of Baylor College of Medicine with the academic rank of assistant professor. He has been involved in basic research since 1991 and has been studying the cellular regulation of beta2AR trafficking since June 1993. He has a strong desire to further develop the essential research skills necessary for a productive academic career. It is hoped that the experience and training gained during the duration of this grant will allow Dr. Moore to become an independent investigator eligible for future NIH funding. Both Drs. Dickey and Knoll hold joint appointments in the Departments of Medicine and Cell Biology, where they are actively involved in teaching programs. These departments exemplify the rich environment in cell and molecular biology at Baylor, with original research of department members regularly appearing in premiere journals, pioneering technologies under development in several laboratories, and a highly competitive graduate school program. Through bench training under the supervision of Drs. Dickey and Knoll, participation in several molecular biology courses in the Baylor Graduate School, weekly attendance of the Cell Biology Research Symposium, and Dr. Richard Clark's weekly laboratory meeting, the candidate will have the opportunity to mature as a basic science investigator in a structured environment.

描述（改编自申请人的摘要） 长期使用β2-肾上腺素能激动剂可能与 哮喘控制恶化和非特异性支气管炎增加 反应能力。 临床状态的恶化可能与 长时间暴露于激动剂后受体致密化。 这 β2-肾上腺素受体（β2-AR）与其效应器腺苷酸环化酶偶联，通过 信号转导Gs蛋白。 通过激动剂结合，可以快速 由于受体磷酸化，受体与其 Gs 蛋白解偶联。 几分钟内，由于内吞作用，膜受体丢失 早期内体。 长时间暴露于激动剂，会丧失 总细胞受体。 候选人已经完成了奖学金 儿科肺病学，目前在贝勒学院任教 医学博士，学术级别为助理教授。 他已经 自1991年起从事基础研究，一直研究细胞 自1993年6月起对beta2AR贩运进行监管。他有一个强烈的愿望 进一步发展生产力所需的基本研究技能 学术生涯。 希望在此期间获得的经验和培训 这笔赠款的期限将使摩尔博士成为一名独立的 研究者有资格获得未来 NIH 资助。 两位博士。迪基和诺尔在以下部门联合任命 医学和细胞生物学，他们积极参与教学 程序。 这些部门体现了细胞和 贝勒大学的分子生物学，以及系成员的原创研究 定期出现在首屈一指的期刊上，开创性技术 多个实验室的发展，以及极具竞争力的毕业生 学校计划。 通过在博士的监督下进行台架训练。迪基 和诺尔，参加贝勒大学的几门分子生物学课程 研究生院，每周参加细胞生物学研究研讨会， 和理查德·克拉克博士的每周实验室会议，候选人将有 作为一名基础科学研究人员在结构化的环境中成熟的机会 环境。