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Rho激酶在细胞死亡与存活调控中的作用

Rho kinase in the regulation of cell death and survival.

作者信息

Shi Jianjian, Wei Lei

机构信息

Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University, School of Medicine, R4 building, Room 370, 1044 West Walnut Str, Indianapolis, IN 46202-5225, USA.

出版信息

Arch Immunol Ther Exp (Warsz). 2007 Mar-Apr;55(2):61-75. doi: 10.1007/s00005-007-0009-7. Epub 2007 Mar 9.

Abstract

Rho kinase (ROCK) belongs to a family of serine/threonine kinases that are activated via interaction with Rho GTPases. ROCK is involved in a wide range of fundamental cellular functions, such as contraction, adhesion, migration, and proliferation. Recent studies have shown that ROCK plays an important role in the regulation of apoptosis in various cell types and animal disease models. Two ROCK isoforms, ROCK1 and ROCK2, are assumed to be function redundant, this based largely on kinase construct overexpression and chemical inhibitors (Y27632 and fasudil) which inhibit both ROCK1 and ROCK2. Gene targeting and RNA interference approaches allow further dissection of distinct cellular, physiological, and patho-physiological functions of the two ROCK isoforms. This review, based on recent molecular, cellular, and animal studies, focuses on the current understanding of ROCK signaling in the regulation of apoptosis and highlights new findings from recently generated ROCK-deficient mice.

摘要

Rho激酶(ROCK)属于丝氨酸/苏氨酸激酶家族,通过与Rho GTP酶相互作用而被激活。ROCK参与多种基本细胞功能,如收缩、黏附、迁移和增殖。最近的研究表明,ROCK在多种细胞类型和动物疾病模型的细胞凋亡调节中起重要作用。两种ROCK亚型,即ROCK1和ROCK2,被认为功能冗余,这主要基于激酶构建体的过表达以及抑制ROCK1和ROCK2的化学抑制剂(Y27632和法舒地尔)。基因靶向和RNA干扰方法有助于进一步剖析两种ROCK亚型不同的细胞、生理和病理生理功能。本综述基于最近的分子、细胞和动物研究,聚焦于当前对ROCK信号在细胞凋亡调节中的理解,并突出了最近产生的ROCK缺陷小鼠的新发现。

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