ROLE OF TRIP6 IN P130CAS SIGNALING AND CELL MOTILITY

TRIP6 在 P130CAS 信号传导和细胞运动中的作用

• 批准号: 6135060
• 负责人: SUSANNE KLOEKER
• 金额: $ 3.24万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-07-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6135060
• 关键词: binding proteins; biological signal transduction; cell motility; cell proliferation; immunocytochemistry; immunoprecipitation; protein protein interaction; protein sequence; protein structure function

The localization of signalling molecules to discrete cellular microenvironments via adaptor or scaffolding proteins is emerging as a paradigm to explain the efficiency and specificity of signal transduction cascades. Thus, proteins involved in organizing these "signalsomes" play a pivotal role in the regulation of intracellular communication. The TRIP6 cDNA encodes a protein with a proline-rich region and three consecutive LIM domains Proline-rich regions have the capacity to interact with Src- homology-3 (SH3) domains and LIM domains also have been characterized as protein/protein interaction motifs. Evidence in Dr. Beckerle's laboratory indicates an association between TRIP6 and another focal adhesion molecule, p130cas. p130cas is a nonenzymatic signalling protein that is tyrosine phosphorylated by Src and focal adhesion kinase in response to integrin- stimulated adhesion and cell migration. Efforts to understand these phenomenon are important because aberrant adhesion and migration can contribute to pathologic physiology such as cancer. In light of these observations, I propose a functional role for TRIP6 as an adaptor protein to coordinate signal transducers involved in integrin-mediated adhesion such as p130cas and other as of yet unidentified proteins. The goal of this proposal plans to determine the relevance of TRIP6 in the regulation of p130cas signalling and cell motility. The aims of this proposal are to 1) map the-binding domains on TRIP6 and p130cas; 2)assess the effects of disrupting the p130cas/TRIP6 interaction, and 3) identify new TRIP6 binding partners.

通过适配器或支架蛋白将信号分子定位于离散的细胞微环境，正在成为解释信号转导级联的效率和特异性的范例。因此，参与组织这些“信号体”的蛋白质在细胞内通讯的调节中起着关键作用。TRIP6编码的蛋白质含有一个富含Pro的区域和三个连续的LIM结构域，富含Pro的区域具有与Src-Homology-3(SH3)结构域相互作用的能力，LIM结构域也被鉴定为蛋白质/蛋白质相互作用基序。贝克勒博士实验室的证据表明，TRIP6和另一种焦点黏附分子p130Cas之间存在关联。P130Cas是一种非酶信号转导蛋白，在整合素刺激的黏附和细胞迁移过程中被Src和粘着斑激酶磷酸化。努力了解这些现象是重要的，因为异常的黏附和迁移可以促进病理生理学，如癌症。根据这些观察，我提出了TRIP6作为接头蛋白的功能，以协调参与整合素介导的黏附的信号转导分子，如p130Cas和其他未知蛋白。这项提案的目标是确定TRIP6在调节p130Cas信号和细胞运动方面的相关性。该建议的目的是1)定位TRIP6和p130Cas上的结合结构域；2)评估破坏p130Cas/TRIP6相互作用的影响；3)寻找新的TRIP6结合伙伴。