Regulation of ROCK serine/threonine kinases by Rnd proteins

Rnd 蛋白对 ROCK 丝氨酸/苏氨酸激酶的调节

• 批准号: BB/E004083/1
• 负责人: Anne Ridley
• 金额: $ 35.79万
• 依托单位: University College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2006
• 资助国家: 英国
• 起止时间: 2006 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FE004083%2F1
• 关键词: Regulation; ROCK; serine; threonine; kinases

In mammals, cells need to move during development, wound healing and in response to infection. Cell movement is driven by the cytoskeleton, principally by filaments made of actin molecules. Part of cell movement involves contractile forces, which are generated by myosin filaments moving along actin filaments. Similar interactions between myosin and actin filaments generate muscle contraction. The ability of myosin filaments to move along actin filaments is increased by a protein called ROCK-I. Several human diseases could be treated by chemicals that inhibit ROCK-I, including heart disease, Alzheimers' disease and some cancers. We have identified a protein in cells, called RhoE, that binds to and inhibits ROCK-I, and thus reduces the interaction of myosin filaments with actin filaments. We want to understand more about how RhoE inhibits ROCK-I, and predict that this will help in the design of new chemicals to inhibit ROCK-I.

在哺乳动物中，细胞在发育、伤口愈合和对感染的反应中需要移动。细胞运动由细胞骨架驱动，主要由肌动蛋白分子构成的细丝驱动。细胞运动的一部分涉及收缩力，收缩力是由肌凝蛋白丝沿着肌动蛋白丝移动而产生的。肌凝蛋白和肌动蛋白丝之间类似的相互作用产生肌肉收缩。肌凝蛋白丝沿着肌动蛋白丝移动的能力是由一种叫做rock - 1的蛋白质增加的。一些人类疾病可以通过抑制rock - 1的化学物质来治疗，包括心脏病、阿尔茨海默病和一些癌症。我们已经在细胞中发现了一种叫做RhoE的蛋白质，它可以结合并抑制ROCK-I，从而减少肌凝蛋白丝与肌动蛋白丝的相互作用。我们希望更多地了解RhoE如何抑制ROCK-I，并预测这将有助于设计抑制ROCK-I的新化学品。

项目成果

Rho GTPases and cancer cell transendothelial migration.

• DOI: 10.1007/978-1-61779-442-1_9
• 发表时间: 2012
• 期刊: Methods in molecular biology
• 作者: Nicolas Reymond;P. Riou;A. Ridley

An antagonistic interaction between PlexinB2 and Rnd3 controls RhoA activity and cortical neuron migration.

• DOI: 10.1038/ncomms4405
• 发表时间: 2014-02-27
• 期刊: NATURE COMMUNICATIONS
• 影响因子: 16.6
• 作者: Azzarelli, Roberta;Pacary, Emilie;Garg, Ritu;Garcez, Patricia;van den Berg, Debbie;Riou, Philippe;Ridley, Anne J.;Friedel, Roland H.;Parsons, Maddy;Guillemot, Francois
• 通讯作者: Guillemot, Francois

Regulation of Rnd3 localization and function by protein kinase C alpha-mediated phosphorylation.

• DOI: 10.1042/bj20082377
• 发表时间: 2009-10-23
• 期刊: The Biochemical journal
• 作者: Madigan JP;Bodemann BO;Brady DC;Dewar BJ;Keller PJ;Leitges M;Philips MR;Ridley AJ;Der CJ;Cox AD
• 通讯作者: Cox AD

Rnd3 induces stress fibres in endothelial cells through RhoB.

• DOI: 10.1242/bio.20123574
• 发表时间: 2013-02-15
• 期刊: Biology open
• 影响因子: 2.4
• 作者: Gottesbühren U;Garg R;Riou P;McColl B;Brayson D;Ridley AJ
• 通讯作者: Ridley AJ

Rnd3-induced cell rounding requires interaction with Plexin-B2.

• DOI: 10.1242/jcs.192211
• 发表时间: 2016-11-01
• 期刊: Journal of cell science
• 影响因子: 4
• 作者: McColl B;Garg R;Riou P;Riento K;Ridley AJ
• 通讯作者: Ridley AJ