Borg regulation and mammalian Septin function

Borg 调节和哺乳动物 Septin 功能

• 批准号: 6752389
• 负责人: CAREY J OLIVER
• 金额: $ 4.73万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-06-01 至 2006-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6752389
• 关键词: 3T3 cells; MDCK cell; SDS polyacrylamide gel electrophoresis; autoradiography; biological signal transduction; cell differentiation; cell growth regulation; cell morphology; cell motility; fluorescence resonance energy transfer; guanine nucleotide binding protein; guanosinetriphosphatases; immunoprecipitation; mass spectrometry; matrix assisted laser desorption ionization; nuclear transfer; phosphorylation; polymerase chain reaction; postdoctoral investigator; protein structure function; site directed mutagenesis; thin layer chromatography; western blottings

DESCRIPTION (provided by applicant): Cdc42, a member of the Rho subfamily of Ras GTPases, is involved in a number of biological pathways, such as cell growth and differentiation, actin cytoskeleton dynamics, and cell motility. To understand how Cdc42 can control these widely different processes, the effector pathways it activates must be examined. One such pathway that has not been extensively studied is Cdc42's activation of the Borg family of proteins. This proposal will examine the mechanisms of Borg regulation and how this regulation impacts on a family of known Borg binding proteins, the mammalian Septins. Specific aim #1 will identify potential signaling pathways involved in Borg regulation, focusing on my recent discovery that Borgs are phosphorylated in vivo. This aim will be accomplished by determining the site(s) phosphorylated on Borgs, the signal transduction cascades that stimulate Borg phosphorylation, and the effect of overexpressing Borg phosphorylation site mutants on its localization and on cell morphology. Specific aim #2 will build on the knowledge obtained in aim #1 to examine the role of Borgs in Septin organization and function. Septins can interact with one another to form filaments. The effect of Borg phosphorylation on its binding to Septins, Septin organization in the cell, and Septin control of cytokinesis will be examined.

描述（由申请人提供）： Cdc42是RAS GTPases的Rho亚家族的成员，参与了许多生物学途径，例如细胞生长和分化，肌动蛋白细胞骨架动力学和细胞运动。要了解CDC42如何控制这些广泛不同的过程，必须检查其激活的效应途径。 Cdc42激活了Borg蛋白质家族的一种尚未进行广泛研究的途径。该提案将检查Borg调节的机制，以及该调节如何影响已知的Borg结合蛋白（哺乳动物Septins）的家族。具体目标＃1将确定与Borg调节有关的潜在信号通路，重点是我最近发现Borgs在体内被磷酸化。 这一目标将通过确定在Borgs上磷酸化的位点，刺激Borg磷酸化的信号转导级联反应以及过表达Borg磷酸化位点突变体对其定位和细胞形态学的影响。特定的目标＃2将基于AIM＃1中获得的知识，以研究Borgs在Septin组织和功能中的作用。 Septins可以相互作用以形成细丝。将检查Borg磷酸化对SEPTIS，细胞中的Septin组织和septin对细胞因子的结合的影响。