Csk, a critical link of g protein signals to actin cytoskeletal reorganization

Dev Cell. 2002 Jun;2(6):733-44. doi: 10.1016/s1534-5807(02)00175-2.

Abstract

Heterotrimeric G proteins can signal to reorganize the actin cytoskeleton, but the mechanism is unclear. Here we report that, in tyrosine kinase Csk-deficient mouse embryonic fibroblast cells, G protein (Gbetagamma, Galpha(12), Galpha(13), and Galpha(q))-induced, and G protein-coupled receptor-induced, actin stress fiber formation was completely blocked. Reintroduction of Csk into Csk-deficent cells restored the G protein-induced actin stress fiber formation. Chemical rescue experiments with catalytic mutants of Csk demonstrated that the catalytic activity of Csk was required for this process. Furthermore, we uncovered that Gbetagamma can both translocate Csk to the plasma membrane and directly increase Csk kinase activity. Our genetic and biochemical studies demonstrate that Csk plays a critical role in mediating G protein signals to actin cytoskeletal reorganization.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3T3 Cells
  • Actins / drug effects
  • Actins / physiology*
  • Animals
  • Biological Transport
  • CSK Tyrosine-Protein Kinase
  • Catalysis
  • Cell Line
  • Cell Membrane / physiology
  • Cytoskeleton / physiology
  • Enzyme Activation
  • Fibroblasts / enzymology
  • Heterotrimeric GTP-Binding Proteins / genetics
  • Heterotrimeric GTP-Binding Proteins / metabolism*
  • Heterotrimeric GTP-Binding Proteins / pharmacology
  • Humans
  • Mice
  • Mice, Knockout
  • Mutation
  • Protein-Tyrosine Kinases
  • Proto-Oncogene Proteins / deficiency
  • Proto-Oncogene Proteins / metabolism*
  • Receptors, Cell Surface / metabolism
  • Receptors, Opioid / metabolism
  • Recombinant Fusion Proteins / metabolism
  • Signal Transduction
  • src-Family Kinases / deficiency
  • src-Family Kinases / metabolism*

Substances

  • Actins
  • Proto-Oncogene Proteins
  • Receptors, Cell Surface
  • Receptors, Opioid
  • Recombinant Fusion Proteins
  • nociceptin receptor
  • Protein-Tyrosine Kinases
  • CSK Tyrosine-Protein Kinase
  • src-Family Kinases
  • CSK protein, human
  • Heterotrimeric GTP-Binding Proteins