U.S.-Japan Cooperative Science: Physiological and Cellular Functions for the Signaling Enzyme Phospholipase D

9909888 Frohman该奖项支持斯托尼布鲁克纽约州立大学的Michael Frohman教授和日本东京工业大学的Yasunori Kanaho教授之间为期两年的合作研究项目。 研究人员将对信号酶磷脂酶D（PLD）的生理和细胞功能进行研究。 PLD是最近鉴定的哺乳动物信号转导子，其被认为在激动剂诱导的细胞反应（包括膜囊泡运输（分泌和内吞作用）、增殖和分化）中起重要作用。 最近的研究在一定程度上证明了PLD的调节机制。 然而，PLD的生理和细胞功能仍有待澄清。 本项目的目的是利用生物化学、分子生物学、细胞生物学和转基因方法确定PLD参与的信号通路和PLD激活的后果。 研究人员将确定PLD激活下游的效应子，并确定在没有PLD的情况下，或者当野生型、显性阴性和组成性激活PLD突变体过度表达时，它们的活性如何变化。 该项目汇集了两个具有互补专业知识和研究能力的实验室的努力。 美国研究人员的专长是分子生物学领域，日本研究人员的专长是生化探针。 研究结果将提供对细胞刺激反应途径的更好理解。 随着这些途径的定义及其代谢中间体的鉴定，随着特定的新药剂的发现，治疗进展正在实现。 本研究通过博士后和研究生的参与促进国际人力资源。 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。 研究人员计划在科学期刊上发表研究结果。

9909888FrohmanThis award supports a two year collaborative research project between Professor Michael Frohman of the State University of New York (SUNY), Stony Brook and Professor Yasunori Kanaho of the Tokyo Institute of Technology in Japan. The researchers will be undertaking a study of the physiological and cellular functions for the signalling enzyme phospholipase D (PLD). PLD is a recently identified mammalian signal transducer that is believed to play important roles in agonist-induced cellular responses including membrane vesicular trafficking (secretion and endocytosis), proliferation, and differentiation. Recent studies have demonstrated to some extent the mechanism through which PLD is regulated. However, the physiological and cellular functions of PLD remain to be clarified. The aims of this project are to determine the signaling pathway(s) in which PLD is involved and the consequence(s) of PLD activation, using biochemical, molecular biological, cell biological, and transgenic approaches. The researchers will identify effectors downstream of PLD activation and determine how their activity changes in the absence of PLD, or when wild type, dominant negative, and constitutively active PLD mutants are over-expressed. The project brings together the efforts of two laboratories that have complementary expertise and research capabilities. The U.S. researchers' expertise is in the area of molecular biology and the Japanese have expertise in biochemical probes. Results of the research will provide a greater understanding of cellular stimulus response pathways. As these pathways are defined and their metabolic intermediates identified, therapeutic advances are being realized as specific new pharmaceutical agents are discovered. This research advances international human resources through the participation of postdocs and graduate students. Through the exchange of ideas and technology, this project will broaden our base of basic knowledge and promote international understanding and cooperation. The researchers plan to publish results of the research in scientific journals.