U.S.-Japan Cooperative Science: Regulation and Roles of Signal Transducing

美日合作科学：信号转导的调控和作用

• 批准号: 9603360
• 负责人: Michael Frohman
• 金额: $ 2.62万
• 依托单位: SUNY at Stony Brook
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-05-01 至 2000-04-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9603360&HistoricalAwards=false
• 关键词: U.S.; Japan; Cooperative; Science; Regulation

9603360 Frohman This award supports a two year collaborative research project between Professor Michael Frohman of the State University of New York (SUNY) at Stony Brook and Professor Yoshinori Nozawa of the Gifu University School of Medicine in Japan. The project will investigate the biochemical, cellular, and physiological roles of Phospholipase D (PLD), an enzyme thought to be involved in signal transduction, vesicular trafficking, and the control of cell division. The major goals of this project are: 1) to continue structure-function experiments using site-directed mutagenesis to identify amino acids required for interaction with cofactors such as protein kinase C and small G- proteins, and intracellular localization; and 2) to determine whether PLD1 or 2 are activated by stimulation of specific signal transduction pathways in well characterized cell lines, and whether such activation is necessary or sufficient to generate the subsequent cellular responses that have been ascribed to PLD activation in general. The project brings together the efforts of two laboratories that have constituted different parts of the process. The Americans have extensive experience with standard and advanced molecular biology techniques, microinjection of plasmids and proteins into cells, embryonic in situ hybridization, and transgenic mouse technology. The Japanese have been using approaches to study PLD for a decade and have extensive experience with a wide variety of pharmacological PLD activators and inhibitors, and with measuring the cellular consequences correlated with PLD activation, such as serotonin secretion, mast cell degranulation, and diacylglycerol production. PLD activation has been linked to a wide variety of normal physiological and disease processes in many different kinds of cells and tissues. Results of the research will provide realistic expectation about the advantages and limitation of the different model systems. This would serve as the basi s to determine which models should be implemented. Through the exchange of ideas and technology, this project will broaden our base of basic knowledge and promote international understanding and cooperation. ***

小行星9603360 该奖项支持纽约州立大学斯托尼布鲁克分校的Michael Frohman教授和日本岐阜大学医学院的Yoshinori Nozawa教授之间为期两年的合作研究项目。 该项目将研究磷脂酶D（PLD）的生化，细胞和生理作用，PLD是一种被认为参与信号转导，囊泡运输和细胞分裂控制的酶。 本项目的主要目标是：1）继续进行结构-功能实验，使用定点突变来鉴定与辅因子如蛋白激酶C和小G蛋白相互作用所需的氨基酸，以及细胞内定位;和2）确定PLD 1或2是否被充分表征的细胞系中的特异性信号转导途径的刺激激活，以及这种激活对于产生通常归因于PLD激活的后续细胞应答是否是必要的或足够的。 该项目汇集了两个实验室的努力，这两个实验室构成了这一过程的不同部分。 美国人在标准和先进的分子生物学技术、质粒和蛋白质显微注射到细胞中、胚胎原位杂交和转基因小鼠技术方面拥有丰富的经验。 日本人已经使用方法来研究PLD十年，并且在各种药理学PLD激活剂和抑制剂以及测量与PLD激活相关的细胞后果（如5-羟色胺分泌、肥大细胞脱粒和二酰基甘油产生）方面具有丰富的经验。 PLD激活与许多不同类型的细胞和组织中的多种正常生理和疾病过程有关。 研究结果将为不同模型系统的优点和局限性提供现实的期望。这将作为确定应实施哪些模型的基础。 通过交流思想和技术，该项目将扩大我们的基础知识，促进国际理解与合作。 ***