Redox-dependent downregulation of Rho by Rac.
Rac and Rho GTPases function as critical regulators of actin cytoskeleton remodelling during cell spreading and migration. Here we demonstrate that Rac-mediated reactive oxygen species (ROS) production results in the downregulation of Rho activity. The redox-dependent decrease in Rho activity is required for Rac-induced formation of membrane ruffles and integrin-mediated cell spreading. The pathway linking generation of ROS to downregulation of Rho involves inhibition of the low-molecular-weight protein tyrosine phosphatase (LMW-PTP) and then an increase in the tyrosine phosphorylation and activation of its target, p190Rho-GAP. Our findings define a novel mechanism for the coupling of changes in cellular redox state to the control of actin cytoskeleton rearrangements by Rho GTPases.
Nimnual
Anjaruwee S
AS
Department of Molecular Genetics and Microbiology, State University of New York at Stony Brook, Stony Brook, NY 11794, USA.
Taylor
Laura J
LJ
Bar-Sagi
Dafna
D
D015536:Down-Regulation; D019204:GTP-Binding Proteins / Q000502:physiology*; D008970:Molecular Weight; D010084:Oxidation-Reduction; D010766:Phosphorylation; D017027:Protein Tyrosine Phosphatases / Q000737:chemistry / Q000378:metabolism*; D017382:Reactive Oxygen Species; D014443:Tyrosine / Q000378:metabolism; D020744:rac GTP-Binding Proteins / Q000502:physiology*
D017382:Reactive Oxygen Species; D014443:Tyrosine; D017027:Protein Tyrosine Phosphatases; D019204:GTP-Binding Proteins; D020744:rac GTP-Binding Proteins