Molecular and Cellular Dynamics in Mammalian Signal Transduction

哺乳动物信号转导中的分子和细胞动力学

• 批准号: 10799380
• 负责人: NATALIE G. AHN
• 金额: $ 5.48万
• 依托单位: UNIVERSITY OF COLORADO
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-01 至 2025-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10799380
• 关键词: Address; Affinity; Cells; Complex; Disease; Dissection; Human; Knowledge; Laboratories; MAPK1 gene; Malignant Neoplasms; Microscopic; Mitogen-Activated Protein Kinases; Molecular; Motion; Names; Organelles; Phosphorylation; Process; Protein Kinase; Proteins; Public Health; Regulation; Research; Signal Transduction; Structure; Work; cell motility; directional cell; human disease; inhibitor; novel therapeutics

PROJECT SUMMARY This MIRA proposal addresses two important avenues of discovery made by our laboratory. In Part 1, we will examine the mechanism of allosteric activation by phosphorylation of the MAP kinase, ERK2. This project advances the protein kinase field, by showing how protein motions underlie the catalytic activation of ERK2 and how this impacts the action of high affinity inhibitors. In Part 2, we will examine the mechanisms controlling the assembly and function of a rear-polarized cellular complex, named the WRAMP structure. The WRAMP structure advances the field of cell motility, as a new mechanism that controls the persistence of directional cell migration and the direction of cell movement. The projects are unified by their dissection of molecular mechanisms that control dynamics in cell signaling. This occurs at a microscopic level by the molecular motions of protein kinases and at a macroscopic level by the assembly of cellular protein-organelle complexes.

项目摘要 MIRA的这一建议涉及我们实验室发现的两个重要途径。在 第一部分，我们将研究磷酸化MAP的变构激活机制 激酶，ERK 2。该项目通过展示蛋白质运动方式， ERK 2的催化活化的基础，以及这如何影响高亲和力的作用， 抑制剂的在第2部分中，我们将研究控制 后极化细胞复合体，命名为WRAMP结构。WRAMP结构的进步 细胞运动领域，作为一种新的机制，控制定向细胞的持久性 迁移和细胞运动的方向。这些项目是统一的解剖 控制细胞信号动态的分子机制。这发生在微观层面 通过蛋白激酶的分子运动，以及在宏观水平上通过 细胞蛋白质-细胞器复合物。

项目成果

Activation loop plasticity and active site coupling in the MAP kinase, ERK2.

MAP 激酶 ERK2 中的激活环可塑性和活性位点耦合。

• DOI: 10.1101/2023.04.15.537040
• 发表时间: 2023
• 期刊: bioRxiv : the preprint server for biology
• 作者: Pegram,Laurel;Riccardi,Demian;Ahn,Natalie
• 通讯作者: Ahn,Natalie