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.
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.
Barwe
S P
SP
Department of Pathology and Laboratory Medicine, University of California, Los Angeles, California 90095, USA.
Rajasekaran
S A
SA
Rajasekaran
A K
AK
D000818:Animals; D017306:Annexin A2 / Q000378:metabolism; D002448:Cell Adhesion; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D004285:Dogs; D004789:Enzyme Activation; D009154:Mutation; D010042:Ouabain / Q000378:metabolism / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D011485:Protein Binding; D011493:Protein Kinase C / Q000502:physiology*; D021122:Protein Subunits / Q000502:physiology; D011554:Pseudopodia / Q000502:physiology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D020830:rac1 GTP-Binding Protein / Q000378:metabolism
D017306:Annexin A2; D010042:Ouabain; D019869:Phosphatidylinositol 3-Kinases; D011493:Protein Kinase C; D021122:Protein Subunits; D000254:Sodium-Potassium-Exchanging ATPase; D020830:rac1 GTP-Binding Protein