SIGNAL TRANSDUCTION BY PROTEIN PHOSPHORYLATION

通过蛋白质磷酸化进行信号转导

• 批准号: 3224544
• 负责人: EDMOND H FISCHER
• 金额: $ 30.23万
• 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/3224544
• 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; 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.

我们建议继续研究细胞过程的调节 通过蛋白质磷酸化，特别是结构、功能和 蛋白酪氨酸磷酸酶（PTP）的调节。 PTP 现在是 已知代表一个大而多样化的细胞内和 受体连接酶。 可以假设它们发挥着重要作用 调节这些激素引发的事件的多样性 具有内在蛋白酪氨酸激酶的生长因子受体 活动并微调调节的高度集成电路 真核细胞。 我们的主要目标是研究： a) 结构、性质 以及细胞内酶和受体相关酶的调节； b) 酪氨酸、丝氨酸和苏氨酸之间必须存在相互作用 磷酸化； c) PTP 的亚细胞定位及其 参与细胞周期和细胞骨架重组；和 d) 它们可能具有阻止或逆转细胞转化的功能。 试图解释磷酸酶如何发挥作用的假设 与激酶协同作用，引发完整的生理反应， 无论目标蛋白的磷酸化状态如何，都会 被测试。