Molecular and Cellular Dynamics in Mammalian Signal Transduction

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。

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.