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Cytoskeletal effects of Rho-like small guanine nucleotide-binding proteins in the vascular system

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Author: Nieuw Amerongen, G.P. van · Hinsbergh, V.W.M. van
Type:article
Date:2001
Institution: Gaubius Instituut TNO
Source:Arteriosclerosis, Thrombosis, and Vascular Biology, 3, 21, 300-311
Identifier: 236006
Keywords: Actins · Animals · Cell Movement · Cytoskeleton · Endothelium, Vascular · Humans · Models, Biological · Muscle, Smooth, Vascular · rho GTP-Binding Proteins · Vasoconstriction

Abstract

Rho-like small GTPases, with their main representatives (Rho, Rac, and Cdc42), have been recognized in the past decade as key regulators of the F-actin cytoskeleton. Rho-like small GTPases are now known to play a major role in vascular processes caused by changes in the actin cytoskeleton, such as smooth muscle cell contraction, endothelial permeability, platelet activation, and leukocyte migration. Data are now accumulating regarding the involvement of Rho GTPases in vascular disorders associated with vascular remodeling, altered cell contractility, and cell migration. The unraveling of signal transduction pathways used by the Rho-like GTPases revealed many upstream regulators and downstream effector molecules, and their number is still growing. An important action of Rho, Rac, and Cdc42 is their ability to regulate the phosphorylation status of the myosin light chain, a major regulator of actin-myosin interaction. Present knowledge of the Rho-like small GTPases has resulted in the development of promising new strategies for the treatment of many vascular disorders, including hypertension, vasospasms, and vascular leakage. Chemicals/CAS: Actins; rho GTP-Binding Proteins, EC 3.6.5.2