Redox-dependent Downregulation of Rho by Rac

Nat Cell Biol. 2003 Mar;5(3):236-41. doi: 10.1038/ncb938.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Down-Regulation*
  • GTP-Binding Proteins / physiology*
  • Molecular Weight
  • Oxidation-Reduction
  • Phosphorylation
  • Protein Tyrosine Phosphatases / chemistry
  • Protein Tyrosine Phosphatases / metabolism*
  • Reactive Oxygen Species
  • Tyrosine / metabolism
  • rac GTP-Binding Proteins / physiology*

Substances

  • Reactive Oxygen Species
  • Tyrosine
  • Protein Tyrosine Phosphatases
  • GTP-Binding Proteins
  • rac GTP-Binding Proteins