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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
38
pubmed:dateCreated
1997-10-23
pubmed:abstractText
In this study, we examined the potential role of serine/threonine protein phosphatase-1 (PP-1) and PP-2A in the mechanism of Na+/K+-ATPase activation by insulin in the rat skeletal muscle cell line L6. Incubation of L6 cells with insulin caused a time- and dose-dependent stimulation of ouabain-sensitive plasma membrane Na+/K+-ATPase activity. Pretreatment with okadaic acid (OA; 0.1-1 microM) or calyculin A (1 microM) blocked insulin's effect on Na+/K+-ATPase activation. Low concentrations of OA that specifically inhibit PP-2A were ineffective. Immunoprecipitation of the enzyme from 32P-labeled cells with an antibody directed against the alpha-1 subunit of the enzyme revealed a 60% decrease in 110-kDa protein phosphorylation in insulin-treated cells. The presence of calyculin A blocked insulin-mediated dephosphorylation of Na+/K+-ATPase, whereas low concentrations of OA were ineffective. To further confirm the role of PP-1, we used L6 cell lines that overexpress the glycogen/SR-associated regulatory subunit of PP-1, PP-1G. Overexpression of PP-1G resulted in a 3-fold increase in insulin-stimulated PP-1 catalytic activity. This was accompanied by a 30% increase in basal Na+/K+-ATPase activity and a >2-fold increase in insulin's effect on pump activity. Inhibition of phosphatidylinositol-3 kinase with wortmannin blocked insulin-stimulated PP-1 activation as well as the dephosphorylation and activation of Na+/K+-ATPase. We conclude that insulin regulates the activity of Na+/K+-ATPase by promoting dephosphorylation of the alpha subunit via an insulin-stimulated PP-1 and that phosphatidylinositol-3 kinase-generated signals may mediate insulin activation of PP-1 and Na+/K+-ATPase.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
19
pubmed:volume
272
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
23653-8
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed:year
1997
pubmed:articleTitle
Role of serine/threonine protein phosphatases in insulin regulation of Na+/K+-ATPase activity in cultured rat skeletal muscle cells.
pubmed:affiliation
The Diabetes Research Laboratory, Winthrop University Hospitol, Mineola, New York 11501, USA.
pubmed:publicationType
Journal Article