Novel Role for Na,K-ATPase in Phosphatidylinositol 3-Kinase Signaling and Suppression of Cell Motility
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Published:2005-03
Issue:3
Volume:16
Page:1082-1094
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ISSN:1059-1524
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Container-title:Molecular Biology of the Cell
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language:en
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Short-container-title:MBoC
Author:
Barwe Sonali P.1, Anilkumar Gopalakrishnapillai1, Moon Sun Y.2, Zheng Yi2, Whitelegge Julian P.3, Rajasekaran Sigrid A.1, Rajasekaran Ayyappan K.1
Affiliation:
1. Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095 2. Division of Experimental Hematology and Molecular Developmental Biology Program, Children's Hospital Research Foundation, University of Cincinnati, Cincinnati, OH 45229 3. Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, CA 90095
Abstract
The Na,K-ATPase, consisting of α- and β-subunits, regulates intracellular ion homeostasis. Recent studies have demonstrated that Na,K-ATPase also regulates epithelial cell tight junction structure and functions. Consistent with an important role in the regulation of epithelial cell structure, both Na,K-ATPase enzyme activity and subunit levels are altered in carcinoma. Previously, we have shown that repletion of Na,K-ATPase β1-subunit (Na,K-β) in highly motile Moloney sarcoma virus-transformed Madin-Darby canine kidney (MSV-MDCK) cells suppressed their motility.However, until now, the mechanism by which Na,K-β reduces cell motility remained elusive. Here, we demonstrate that Na,K-β localizes to lamellipodia and suppresses cell motility by a novel signaling mechanism involving a cross-talk between Na,K-ATPase α1-subunit (Na,K-α) and Na,K-β with proteins involved in phosphatidylinositol 3-kinase (PI3-kinase) signaling pathway. We show that Na,K-α associates with the regulatory subunit of PI3-kinase and Na,K-β binds to annexin II. These molecular interactions locally activate PI3-kinase at the lamellipodia and suppress cell motility in MSV-MDCK cells, independent of Na,K-ATPase ion transport activity. Thus, these results demonstrate a new role for Na,K-ATPase in regulating carcinoma cell motility.
Publisher
American Society for Cell Biology (ASCB)
Subject
Cell Biology,Molecular Biology
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