Identification of protein kinase C as an intermediate in Na,K-ATPase beta-subunit mediated lamellipodia formation and suppression of cell motility in carcinoma cells

Cell Mol Biol (Noisy-le-grand). 2006 Dec 30;52(8):41-7.

Abstract

We have shown that repletion of Na,K-ATPase Beta1-subunit (Na,K-Beta) in Moloney Sarcoma virus transformed MDCK (MSV-Na,K-Beta) cells induced lamellipodia and suppressed motility in a PI3-Kinase dependent manner. In this study, we provide evidence that decreased cell motility is due to increased attachment of Na,K-Beta expressing cells to the substratum. Treatment of MSV-Beta-GFP cells with bisindolylmalemide, a general Protein Kinase C (PKC) inhibitor, abolished PI3-Kinase activation and its down stream effects of Rac1 activation, binding of Na,K-Beta to annexin II, and suppression of cell motility and attachment. Thus, these studies unraveled that a PKC is involved upstream of PI3-Kinase in the suppression of Na,K-Beta mediated cell motility in carcinoma cells.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Annexin A2 / metabolism
  • Cell Adhesion
  • Cell Line, Transformed
  • Cell Line, Tumor
  • Cell Movement / physiology*
  • Dogs
  • Enzyme Activation
  • Mutation
  • Ouabain / metabolism
  • Ouabain / pharmacology
  • Phosphatidylinositol 3-Kinases / physiology*
  • Protein Binding
  • Protein Kinase C / physiology*
  • Protein Subunits / physiology
  • Pseudopodia / physiology*
  • Sodium-Potassium-Exchanging ATPase / antagonists & inhibitors
  • Sodium-Potassium-Exchanging ATPase / genetics
  • Sodium-Potassium-Exchanging ATPase / physiology*
  • rac1 GTP-Binding Protein / metabolism

Substances

  • Annexin A2
  • Protein Subunits
  • Ouabain
  • Protein Kinase C
  • rac1 GTP-Binding Protein
  • Sodium-Potassium-Exchanging ATPase