Abstract
Rho-associated kinases ROCK1 and ROCK2 are key regulators of actin cytoskeleton dynamics downstream of Rho GTPases that participate in the control of important physiologic functions, S including cell contraction, migration, proliferation, adhesion, and inflammation. Several excellent review articles dealing with ROCK function and regulation have been published over the past few years. Although a brief overview of general molecular, biochemical, and functional properties of ROCKs is included, an effort has been made to produce an original work by collecting and synthesizing recent studies aimed at translating basic discoveries from cell and experimental models into knowledge of human physiology, pathophysiological mechanisms, and medical therapeutics. This review points out the specificity and distinct roles of ROCK1 and ROCK2 isoforms highlighted in the last few years. Results obtained from genetically modified mice and genetic analysis in humans are discussed. This review also addresses the involvement of ROCKs in human diseases and the potential use of ROCK activity as a biomarker or a pharmacological target for specific inhibitors.
Footnotes
This research was supported by the Institut National de la Santé et de la Recherche Médicale, the French Agence Nationale de la Recherche [Grant ANR-11-BSV1-013-01], and the Fondation de France [Grant 2013 00038590].
- Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics
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- I. Introduction
- II. Rho-Associated Kinase Activity, Targets, and Roles
- III. Lessons from Animal Models of Rho-Associated Kinase Deletion
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- V. Rho-Associated Kinase Activity or Expression: Candidate Biomarker of Human Diseases
- VI. Pharmacological Rho-Associated Kinase Inhibitors
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