Rac regulates phosphorylation of the myosin-II heavy chain, actinomyosin disassembly and cell spreading

Nat Cell Biol. 1999 Aug;1(4):242-8. doi: 10.1038/12068.

Abstract

GTPases of the Rho family regulate actinomyosin-based contraction in non-muscle cells. Activation of Rho increases contractility, leading to cell rounding and neurite retraction in neuronal cell lines. Activation of Rac promotes cell spreading and interferes with Rho-mediated cell rounding. Here we show that activation of Rac may antagonize Rho by regulating phosphorylation of the myosin-II heavy chain. Stimulation of PC12 cells or N1E-115 neuroblastoma cells with bradykinin induces phosphorylation of threonine residues in the myosin-II heavy chain; this phosphorylation is Ca2+ dependent and regulated by Rac. Both bradykinin-mediated and constitutive activation of Rac promote cell spreading, accompanied by a loss of cortical myosin II. Our results identify the myosin-II heavy chain as a new target of Rac-regulated kinase pathways, and implicate Rac as a Rho antagonist during myosin-II-dependent cell-shape changes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actomyosin / metabolism*
  • Animals
  • Bradykinin / pharmacology
  • Calcium / metabolism
  • Cell Line
  • Cell Size / physiology
  • Mice
  • Myosin Heavy Chains / metabolism*
  • PC12 Cells
  • Phosphorylation
  • Protein-Serine-Threonine Kinases / metabolism
  • Rats
  • Signal Transduction
  • rac GTP-Binding Proteins / metabolism*
  • rho GTP-Binding Proteins / metabolism

Substances

  • Actomyosin
  • Protein-Serine-Threonine Kinases
  • Myosin Heavy Chains
  • rac GTP-Binding Proteins
  • rho GTP-Binding Proteins
  • Bradykinin
  • Calcium