Rho激酶在胚胎发育和干细胞研究中的作用

IF 2.9 4区 医学 Q3 IMMUNOLOGY Archivum Immunologiae et Therapiae Experimentalis Pub Date : 2022-01-19 DOI:10.1007/s00005-022-00642-z
Jianjian Shi, Lei Wei
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引用次数: 7

摘要

Rho相关的含Rho激酶(ROCKs或Rho激酶)属于AGC (PKA/PKG/PKC)丝氨酸/苏氨酸激酶家族,是小GTPase RhoA的主要下游效应物,是肌动蛋白-细胞骨架重组的关键调节因子。ROCK家族包含两个成员ROCK1和ROCK2,它们在激酶结构域上具有65%的同源性和92%的同源性。ROCK1和ROCK2被认为在功能上是冗余的,这主要基于它们的主要共同激活因子、高度激酶结构域同源性以及与激酶构建物或化学抑制剂过表达的研究结果。ROCK信号研究自1996年被发现以来,已经扩展到生物学和医学的各个领域。这种快速的进展与ROCK在调节各种细胞行为(如收缩、粘附、迁移、增殖、极性、细胞质分裂和分化)方面的多功能功能相适应。与临床医学的广泛联系,包括心血管异常、异常免疫反应和癌症的发展和转移,显著推动了这一快速进展。在过去的十年中,包括CRISPR-Cas和单细胞组学在内的新型生物技术进一步推动了这一快速发展。目前主要来自基因靶向和RNA干扰方法的共识是,这两种ROCK亚型具有重叠和不同的细胞、生理和病理生理作用。在这篇综述中,我们介绍了岩石研究的里程碑式发现的概述。然后,我们将重点关注胚胎发育中ROCK信号的当前理解,使用敲除和敲入小鼠模型的当前研究现状,以及干细胞研究。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Rho Kinases in Embryonic Development and Stem Cell Research

The Rho-associated coiled-coil containing kinases (ROCKs or Rho kinases) belong to the AGC (PKA/PKG/PKC) family of serine/threonine kinases and are major downstream effectors of small GTPase RhoA, a key regulator of actin-cytoskeleton reorganization. The ROCK family contains two members, ROCK1 and ROCK2, which share 65% overall identity and 92% identity in kinase domain. ROCK1 and ROCK2 were assumed to be functionally redundant, based largely on their major common activators, their high degree kinase domain homology, and study results from overexpression with kinase constructs or chemical inhibitors. ROCK signaling research has expanded to all areas of biology and medicine since its discovery in 1996. The rapid advance is befitting ROCK’s versatile functions in modulating various cell behavior, such as contraction, adhesion, migration, proliferation, polarity, cytokinesis, and differentiation. The rapid advance is noticeably driven by an extensive linking with clinical medicine, including cardiovascular abnormalities, aberrant immune responsive, and cancer development and metastasis. The rapid advance during the past decade is further powered by novel biotechnologies including CRISPR-Cas and single cell omics. Current consensus, derived mainly from gene targeting and RNA interference approaches, is that the two ROCK isoforms have overlapping and distinct cellular, physiological and pathophysiology roles. In this review, we present an overview of the milestone discoveries in ROCK research. We then focus on the current understanding of ROCK signaling in embryonic development, current research status using knockout and knockin mouse models, and stem cell research.

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来源期刊
CiteScore
5.90
自引率
0.00%
发文量
26
审稿时长
>12 weeks
期刊介绍: Archivum Immunologiae et Therapiae Experimentalis (AITE), founded in 1953 by Ludwik Hirszfeld, is a bimonthly, multidisciplinary journal. It publishes reviews and full original papers dealing with immunology, experimental therapy, immunogenetics, transplantation, microbiology, immunochemistry and ethics in science.
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