p190 RhoGAP Regulation and Function

p190 RhoGAP 调节和功能

• 批准号: 7269207
• 负责人: JENNIFER A LAMB
• 金额: $ 1.01万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-30 至 2008-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7269207
• 关键词: actins; biological signal transduction; cell component structure /function; cell migration; cell motility; cellular oncology; cytoskeleton; electron microscopy; embryogenesis; fluorescence microscopy; genetically modified animals; guanine nucleotide binding protein; laboratory mouse; ligands; microfluidics; molecular /cellular imaging; molecular oncology; neoplastic transformation; postdoctoral investigator; protein structure function; transport proteins

DESCRIPTION (provided by applicant): Actin remodeling at the plasma membrane is required for cell migration. The Ena/VASP family of actin regulatory proteins are key regulators of filopodia and lamellipodia dynamics, both environment sensing protrusions involved in migration. These proteins are potential convergent points for second messenger pathways. Lamellipodin (Lpd) is an Ena/VASP ligand recently identified in the Gertler laboratory. Lamellipodin (Lpd) is discretely targeted to the leading edge of lamellipodia and the tips of filopodia. Knockdown of Lpd expression causes defects in lamellipodia formation and alters F-actin geometry and content with the cell. Lpd contains a RAS-association (RA) domain. RA domains mediate binding to specific members of the RAS subfamily of small GTPases. RAS signaling can induce changes in cell polarity and motility and drive oncogenic transformation. We hypothesize that Lpd couples signaling by RAS proteins to cytoskeletal dynamics. The goal of this proposal is to elucidate the underlying molecular mechanisms for Lpd function by addressing the general hypothesis that Lpd transduces signals from the RAS family proteins to regulate cell migration by regulating actin dynamics, in part via Ena/VASP proteins.

描述（由申请人提供）：细胞迁移需要在质膜处进行肌动蛋白重塑。肌动蛋白调节蛋白的ENA/VASP家族是丝状动态和片状脂蛋白动力学的关键调节剂，这两种环境感应迁移的环境传感突出。这些蛋白质是第二信使途径的潜在收敛点。 Lamellipodin（LPD）是最近在Gertler实验室中发现的ENA/VASP配体。层lamelipodin（LPD）离散地针对薄片的前缘和丝状尖端。 LPD表达的敲低导致层状脂蛋白形成的缺陷，并改变F-肌动蛋白的几何形状并与细胞含量。 LPD包含一个RAS-COSCIATION（RA）结构域。 RA结构域介导与小GTPase的Ras亚家族的特定成员的结合。 RAS信号传导可以诱导细胞极性和运动性的变化，并驱动致癌转化。我们假设RAS蛋白对细胞骨架动力学的LPD伴侣信号传导。该提案的目的是通过解决LPD的总体假设来阐明LPD功能的基本分子机制，即LPD从RAS家族蛋白转导信号来通过ENA/VASP蛋白来调节肌动蛋白动力学来调节细胞迁移。