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: 6518850
• 负责人: SUSANNE KLOEKER
• 金额: $ 2.31万
• 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/6518850
• 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.

信号分子通过接头或支架蛋白定位到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 cDNA编码一个富含脯氨酸区域的蛋白质和三个连续的LIM结构域脯氨酸区域具有与Src- homology-3 （SH3）结构域相互作用的能力，LIM结构域也被表征为蛋白质/蛋白质相互作用的基序。Beckerle博士实验室的证据表明，TRIP6与另一种黏附分子p130cas之间存在关联。p130cas是一种非酶促信号蛋白，在整合素刺激的粘附和细胞迁移过程中被Src和黏附激酶酪氨酸磷酸化。努力了解这些现象是重要的，因为异常的粘附和迁移可以促进病理生理，如癌症。根据这些观察结果，我提出TRIP6作为一种衔接蛋白的功能作用，以协调参与整合素介导的粘附的信号转导，如p130cas和其他尚未确定的蛋白质。本提案的目标是确定TRIP6在p130cas信号传导和细胞运动调节中的相关性。本提案的目的是1)绘制TRIP6和p130cas上的结合域；2)评估破坏p130cas/TRIP6相互作用的影响，3)识别新的TRIP6结合伙伴。