Abstract
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.
We thank our colleagues Astrid Hoeppner, Georg Groth, Cordula Kruse, Sander H. Smits, and Jürgen Scheller for their support and the discussions. We apologize for not being able to cite all the relevant publications due to space limits. We gratefully acknowledge the support and training from the International NRW Research School BioStruct, granted by the Ministry of Innovation, Science and Research of the State North Rhine-Westphalia, the Heinrich-Heine-University of Düsseldorf, and the Entrepreneur Foundation at the Heinrich-Heine-University of Düsseldorf. We also thank the Research Committee of the Medical Faculty of the Heinrich-Heine University of Düsseldorf, the NGFNplus program of the German Ministry of Science and Education (BMBF; grant 01GS08100), USA National Institutes of Health grant R01GM086457 and the International Research Training Group 1902 (IRGT1902) of the German Research Foundation (DFG).
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