Rho-kinase: regulation, (dys) function, and inhibition

被引:138
作者
Amin, Ehsan [1 ]
Dubey, Badri Nath [1 ]
Zhang, Si-Cai [1 ]
Gremer, Lothar [2 ,3 ]
Dvorsky, Radovan [1 ]
Moll, Jens M. [1 ]
Taha, Mohamed S. [1 ]
Nagel-Steger, Luitgard [2 ,3 ]
Piekorz, Roland P. [1 ]
Somlyo, Avril V. [4 ]
Ahmadian, Mohammad R. [1 ]
机构
[1] Univ Dusseldorf, Inst Biochem & Mol Biol 2, Fak Med, D-40255 Dusseldorf, Germany
[2] Forschungszentrum Julich, Inst Strukturbiochem ICS 6, D-52425 Julich, Germany
[3] Univ Dusseldorf, Inst Phys Biol, Math Nat Wissensch Fak, D-40255 Dusseldorf, Germany
[4] Univ Virginia, Dept Mol Physiol & Biol Phys, Charlottesville, VA 22908 USA
基金
美国国家卫生研究院;
关键词
coiled-coil-containing protein kinase; drug target; RhoA; Rho-associated; Rho-kinase; ROCK; VASCULAR SMOOTH-MUSCLE; GERANYLGERANYLTRANSFERASE I INHIBITORS; NUCLEOTIDE-EXCHANGE FACTORS; HETEROTRIMERIC G-PROTEINS; PLURIPOTENT STEM-CELLS; STRESS FIBER FORMATION; NONMUSCLE MYOSIN-II; CENTROSOME DUPLICATION; SIGNAL-TRANSDUCTION; THERAPEUTIC TARGET;
D O I
10.1515/hsz-2013-0181
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
In a variety of normal and pathological cell types, Rho-kinases I and II (ROCKI/II) play a pivotal role in the organization of the nonmuscle and smooth muscle cytoskeleton and adhesion plaques as well as in the regulation of transcription factors. Thus, ROCKI/II activity regulates cellular contraction, motility, morphology, polarity, cell division, and gene expression. Emerging evidence suggests that dysregulation of the Rho-ROCK pathways at different stages is linked to cardiovascular, metabolic, and neurodegenerative diseases as well as cancer. This review focuses on the current status of understanding the multiple functions of Rho-ROCK signaling pathways and various modes of regulation of Rho-ROCK activity, thereby orchestrating a concerted functional response.
引用
收藏
页码:1399 / 1410
页数:12
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