Molecular and Cellular Dynamics in Mammalian Signal Transduction

项目总结 米拉的这项建议解决了我们实验室发现的两个重要途径。在……里面 第一部分，我们将研究MAP的磷酸化激活变构的机制。 激酶、ERK2。这个项目通过展示蛋白质是如何运动的，推动了蛋白激酶领域的发展。 ERK2的催化激活及其对高亲和力作用的影响 抑制剂。在第2部分中，我们将研究控制 背面极化的细胞复合体，称为WRAMP结构。WRAMP结构的进展 细胞运动场，作为一种控制定向细胞持续性的新机制 迁移和细胞运动的方向。这些项目通过对它们的剖析而统一起来 控制细胞信号传递动力学的分子机制。这发生在微观层面上。 通过蛋白激酶的分子运动，以及在宏观水平上通过组装 细胞蛋白质-细胞器复合体。

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.