Rho相关卷曲螺旋结构域蛋白激酶（ROCK）：结构、调节及功能
Rho-associated coiled-coil containing kinases (ROCK): structure, regulation, and functions.
作者信息
Julian Linda, Olson Michael F
机构信息
Beatson Institute for Cancer Research; Glasgow, UK.
出版信息
Small GTPases. 2014;5:e29846. doi: 10.4161/sgtp.29846. Epub 2014 Jul 10.
Abstract
Rho-associated coiled-coil containing kinases (ROCK) were originally identified as effectors of the RhoA small GTPase. (1)(-) (5) They belong to the AGC family of serine/threonine kinases (6) and play vital roles in facilitating actomyosin cytoskeleton contractility downstream of RhoA and RhoC activation. Since their discovery, ROCK kinases have been extensively studied, unveiling their manifold functions in processes including cell contraction, migration, apoptosis, survival, and proliferation. Two mammalian ROCK homologs have been identified, ROCK1 (also called ROCK I, ROKβ, Rho-kinase β, or p160ROCK) and ROCK2 (also known as ROCK II, ROKα, or Rho kinase), hereafter collectively referred to as ROCK. In this review, we will focus on the structure, regulation, and functions of ROCK.
摘要
Rho相关卷曲螺旋结构域蛋白激酶（ROCK）最初被鉴定为RhoA小GTP酶的效应器。（1）（-）（5）它们属于丝氨酸/苏氨酸激酶的AGC家族（6），在RhoA和RhoC激活下游促进肌动球蛋白细胞骨架收缩中发挥重要作用。自发现以来，ROCK激酶已得到广泛研究，揭示了它们在细胞收缩、迁移、凋亡、存活和增殖等过程中的多种功能。已鉴定出两种哺乳动物ROCK同源物，ROCK1（也称为ROCK I、ROKβ、Rho激酶β或p160ROCK）和ROCK2（也称为ROCK II、ROKα或Rho激酶），以下统称为ROCK。在本综述中，我们将重点关注ROCK的结构、调节和功能。
相似文献
1
Rho-associated coiled-coil containing kinases (ROCK): structure, regulation, and functions.
Small GTPases. 2014;5:e29846. doi: 10.4161/sgtp.29846. Epub 2014 Jul 10.
2
Targeting ROCK signaling in health, malignant and non-malignant diseases.
Immunol Lett. 2020 Mar;219:15-26. doi: 10.1016/j.imlet.2019.12.012. Epub 2020 Jan 3.
3
Rho kinase collaborates with p21-activated kinase to regulate actin polymerization and contraction in airway smooth muscle.
J Physiol. 2018 Aug;596(16):3617-3635. doi: 10.1113/JP275751. Epub 2018 Jun 24.
4
Rho-associated coiled-coil kinase (ROCK) signaling and disease.
Crit Rev Biochem Mol Biol. 2013 Jul-Aug;48(4):301-16. doi: 10.3109/10409238.2013.786671. Epub 2013 Apr 19.
5
Rho Kinases in Embryonic Development and Stem Cell Research.
Arch Immunol Ther Exp (Warsz). 2022 Jan 19;70(1):4. doi: 10.1007/s00005-022-00642-z.
6
A molecular ruler regulates cytoskeletal remodelling by the Rho kinases.
Nat Commun. 2015 Dec 1;6:10029. doi: 10.1038/ncomms10029.
7
The GTP binding proteins Gem and Rad are negative regulators of the Rho-Rho kinase pathway.
J Cell Biol. 2002 Apr 15;157(2):291-302. doi: 10.1083/jcb.200111026.
8
A role for the Rho-p160 Rho coiled-coil kinase axis in the chemokine stromal cell-derived factor-1alpha-induced lymphocyte actomyosin and microtubular organization and chemotaxis.
J Immunol. 2002 Jan 1;168(1):400-10. doi: 10.4049/jimmunol.168.1.400.
9
Novel Insights into the Roles of Rho Kinase in Cancer.
Arch Immunol Ther Exp (Warsz). 2016 Aug;64(4):259-78. doi: 10.1007/s00005-015-0382-6. Epub 2016 Jan 2.
10
p116Rip targets myosin phosphatase to the actin cytoskeleton and is essential for RhoA/ROCK-regulated neuritogenesis.
Mol Biol Cell. 2004 Dec;15(12):5516-27. doi: 10.1091/mbc.e04-04-0275. Epub 2004 Oct 6.
引用本文的文献
1
Dual-Targeting of ATOX1 and ROCK1: A Potent Strategy to Potentiate the Inhibition of Lung Adenocarcinoma Proliferation.
Cancers (Basel). 2025 Sep 2;17(17):2887. doi: 10.3390/cancers17172887.
2
A Comprehensive Review of the Role of Rho-Kinase Inhibitors in Corneal Diseases.
Life (Basel). 2025 Aug 13;15(8):1283. doi: 10.3390/life15081283.
3
Comprehensive analysis of regulated cell death pathways: intrinsic disorder, protein-protein interactions, and cross-pathway communication.
Apoptosis. 2025 Aug 19. doi: 10.1007/s10495-025-02161-6.
4
Cellular Responses to Nanoscale Topography Mediated Through the RhoA/ROCK Pathway.
Small. 2025 Aug 18:e05685. doi: 10.1002/smll.202505685.
5
Therapeutic Potential of Rho Kinase Inhibitors in Corneal Disease: A Systematic Review of Preclinical and Clinical Studies.
Biomedicines. 2025 Jun 30;13(7):1602. doi: 10.3390/biomedicines13071602.
6
Research progress of ECT2 and RhoA-related signaling pathways in gynecological tumors.
Front Cell Dev Biol. 2025 Jun 27;13:1602649. doi: 10.3389/fcell.2025.1602649. eCollection 2025.
7
Safety, Tolerability, and Pharmacokinetics of NRL-1049, a Rho-Associated Kinase Inhibitor, in Healthy Volunteers: A Phase 1, First-in-Human, Single-Ascending Dose, Randomized, Placebo-Controlled Trial.
CNS Drugs. 2025 Jul 8. doi: 10.1007/s40263-025-01198-0.
8
Obesity Affects IVF Outcomes and Mevalonic Acid Rescues the Side Effects of Statins on Follicle Growth.
FASEB J. 2025 Jul 15;39(13):e70785. doi: 10.1096/fj.202500914R.
9
Calcium Signaling Dynamics in Vascular Cells and Their Dysregulation in Vascular Disease.
Biomolecules. 2025 Jun 18;15(6):892. doi: 10.3390/biom15060892.
10
USP35 promotes hepatocellular carcinoma proliferation through GASC1-mediated ROCK2 upregulation.
Transl Oncol. 2025 Aug;58:102430. doi: 10.1016/j.tranon.2025.102430. Epub 2025 May 26.
本文引用的文献
1
ROCK1 isoform-specific deletion reveals a role for diet-induced insulin resistance.
Am J Physiol Endocrinol Metab. 2014 Feb;306(3):E332-43. doi: 10.1152/ajpendo.00619.2013. Epub 2013 Dec 10.
2
Ser1333 phosphorylation indicates ROCKI activation.
J Biomed Sci. 2013 Oct 29;20(1):83. doi: 10.1186/1423-0127-20-83.
3
Crucial role of ROCK2 in vascular smooth muscle cells for hypoxia-induced pulmonary hypertension in mice.
Arterioscler Thromb Vasc Biol. 2013 Dec;33(12):2780-91. doi: 10.1161/ATVBAHA.113.301357. Epub 2013 Oct 17.
4
Rap1 potentiates endothelial cell junctions by spatially controlling myosin II activity and actin organization.
J Cell Biol. 2013 Sep 16;202(6):901-16. doi: 10.1083/jcb.201301115. Epub 2013 Sep 9.
5
Identification of ROCK1 kinase as a critical regulator of Beclin1-mediated autophagy during metabolic stress.
Nat Commun. 2013;4:2189. doi: 10.1038/ncomms3189.
6
Blebs produced by actin-myosin contraction during apoptosis release damage-associated molecular pattern proteins before secondary necrosis occurs.
Cell Death Differ. 2013 Oct;20(10):1293-305. doi: 10.1038/cdd.2013.69. Epub 2013 Jun 21.
7
Mechanosensitivity and compositional dynamics of cell-matrix adhesions.
EMBO Rep. 2013 Jun;14(6):509-19. doi: 10.1038/embor.2013.49. Epub 2013 May 17.
8
Reduced LIMK2 expression in colorectal cancer reflects its role in limiting stem cell proliferation.
Gut. 2014 Mar;63(3):480-93. doi: 10.1136/gutjnl-2012-303883. Epub 2013 Apr 12.
9
Distinct roles for ROCK1 and ROCK2 in the regulation of cell detachment.
Cell Death Dis. 2013 Feb 7;4(2):e483. doi: 10.1038/cddis.2013.10.
10
FHL2 prevents cardiac hypertrophy in mice with cardiac-specific deletion of ROCK2.
FASEB J. 2013 Apr;27(4):1439-49. doi: 10.1096/fj.12-217018. Epub 2012 Dec 27.
Zotero 插件