SIGNAL TRANSDUCTION BY PROTEIN PHOSPHORYLATION

通过蛋白质磷酸化进行信号转导

• 批准号: 2135423
• 负责人: EDMOND H FISCHER
• 金额: $ 31.54万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 1978
• 资助国家: 美国
• 起止时间: 1978-09-01 至 1996-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2135423
• 关键词: affinity chromatography; biological signal transduction; cell cycle; enzyme mechanism; enzyme structure; genetically modified animals; growth factor; hormone receptor; hormone regulation /control mechanism; human tissue; immunochemistry; laboratory mouse; laboratory rabbit; mutant; nucleic acid sequence; phosphatase inhibitor; phosphoprotein phosphatase; phosphorylase phosphatase; phosphoserine; placenta; protein sequence; protein structure function; protein tyrosine kinase; threonine; tissue /cell culture

We propose to continue our studies o the regulation of cellular processes by protein phosphorylation, particularly on the structure, function and regulation of protein tyrosine phosphatase (PTPs). The PTPs are now known to represent a large and diverse family of intracellular and receptor-linked enzymes. It can be assumed they play an essential role in regulating the multiplicity of events initiated by those hormone and growth factor receptors possessing intrinsic protein tyrosine kinase activity and in fine-tuning the highly integrated circuits that regulate eukaryotic cells. Our main goal is to study: a) structure, properties and regulation of the intracellular and receptor-linked enzymes; b) interplay that must exist between tyrosine and serine and threonine phosphorylation; c) subcellular localization of the PTPs and their involvement in the cell cycle and cytoskeleton reorganization; and d) their possible function in blocking or reversing cell transformation. A hypothesis attempting to explain how phosphatases might act synergistically with the kinases to elicit a full physiological response, irrespective of the state of phosphorylation of the target protein, will be tested.

我们建议继续我们对细胞过程调节的研究。 通过蛋白质磷酸化，特别是对结构、功能和 蛋白酪氨酸磷酸酶(PTPs)的调节。PTP现在是 已知代表了一个庞大而多样的细胞内和 受体连接的酶。可以认为它们扮演着至关重要的角色。 在调节由这些荷尔蒙和 具有固有蛋白酪氨酸激酶的生长因子受体 活动和微调高度集成的电路来调节 真核细胞。我们的主要目标是研究：a)结构、性能 以及调节细胞内和受体连接的酶；b) 酪氨酸、丝氨酸和苏氨酸之间必须存在的相互作用 磷酸化；c)PTPs及其蛋白的亚细胞定位 参与细胞周期和细胞骨架重组；以及d) 它们可能在阻断或逆转细胞转化中发挥作用。 一种试图解释磷酸酶如何发挥作用的假说 与激活酶协同作用以引起全面的生理反应， 无论目标蛋白的磷酸化状态如何，Will 接受测试。