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

Biol Chem. 2013 Nov;394(11):1399-410. doi: 10.1515/hsz-2013-0181.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Apoptosis / physiology
  • Cell Proliferation
  • Down-Regulation / genetics
  • Down-Regulation / physiology
  • Gene Expression Regulation, Enzymologic / genetics
  • Gene Expression Regulation, Enzymologic / physiology
  • Humans
  • Nitric Oxide Synthase Type III / antagonists & inhibitors
  • Nitric Oxide Synthase Type III / metabolism
  • Phosphorylation / genetics
  • Phosphorylation / physiology
  • Protein Stability
  • Signal Transduction / genetics
  • Signal Transduction / physiology
  • rho GTP-Binding Proteins / physiology
  • rho-Associated Kinases / antagonists & inhibitors*
  • rho-Associated Kinases / metabolism*
  • rho-Associated Kinases / physiology
  • rhoA GTP-Binding Protein / physiology
  • rhoB GTP-Binding Protein / physiology
  • rhoC GTP-Binding Protein

Substances

  • RHOA protein, human
  • NOS3 protein, human
  • Nitric Oxide Synthase Type III
  • rho-Associated Kinases
  • RHOC protein, human
  • rho GTP-Binding Proteins
  • rhoA GTP-Binding Protein
  • rhoB GTP-Binding Protein
  • rhoC GTP-Binding Protein