Insulin-induced stimulation of Na+,K(+)-ATPase activity in kidney proximal tubule cells depends on phosphorylation of the alpha-subunit at Tyr-10

Details

Serval ID
serval:BIB_84C3F71FBF0F
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Insulin-induced stimulation of Na+,K(+)-ATPase activity in kidney proximal tubule cells depends on phosphorylation of the alpha-subunit at Tyr-10
Journal
Molecular Biology of the Cell
Author(s)
Feraille  E., Carranza  M. L., Gonin  S., Beguin  P., Pedemonte  C., Rousselot  M., Caverzasio  J., Geering  K., Martin  P. Y., Favre  H.
ISSN
1059-1524 (Print)
Publication state
Published
Issued date
09/1999
Volume
10
Number
9
Pages
2847-59
Notes
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S. --- Old month value: Sep
Abstract
Phosphorylation of the alpha-subunit of Na+,K(+)-ATPase plays an important role in the regulation of this pump. Recent studies suggest that insulin, known to increase solute and fluid reabsorption in mammalian proximal convoluted tubule (PCT), is stimulating Na+,K(+)-ATPase activity through the tyrosine phosphorylation process. This study was therefore undertaken to evaluate the role of tyrosine phosphorylation of the Na+,K(+)-ATPase alpha-subunit in the action of insulin. In rat PCT, insulin and orthovanadate (a tyrosine phosphatase inhibitor) increased tyrosine phosphorylation level of the alpha-subunit more than twofold. Their effects were not additive, suggesting a common mechanism of action. Insulin-induced tyrosine phosphorylation was prevented by genistein, a tyrosine kinase inhibitor. The site of tyrosine phosphorylation was identified on Tyr-10 by controlled trypsinolysis in rat PCTs and by site-directed mutagenesis in opossum kidney cells transfected with rat alpha-subunit. The functional relevance of Tyr-10 phosphorylation was assessed by 1) the abolition of insulin-induced stimulation of the ouabain-sensitive (86)Rb uptake in opossum kidney cells expressing mutant rat alpha1-subunits wherein tyrosine was replaced by alanine or glutamine; and 2) the similarity of the time course and dose dependency of the insulin-induced increase in ouabain-sensitive (86)Rb uptake and tyrosine phosphorylation. These findings indicate that phosphorylation of the Na+,K(+)-ATPase alpha-subunit at Tyr-10 likely participates in the physiological control of sodium reabsorption in PCT.
Keywords
Amino Acid Substitution Animals Cells, Cultured Enzyme Activation/drug effects Genistein/pharmacology Insulin/*pharmacology Insulin Antagonists/pharmacology Kidney Tubules, Proximal/cytology/drug effects/*enzymology Male Na(+)-K(+)-Exchanging ATPase/antagonists & inhibitors/chemistry/*metabolism Opossums Ouabain/pharmacology Phosphorylation/drug effects Phosphotyrosine/*metabolism Protein Kinase Inhibitors Protein Kinases/metabolism Rats Rats, Wistar Transfection Tyrosine/genetics/metabolism Vanadates/pharmacology
Pubmed
Web of science
Create date
24/01/2008 12:28
Last modification date
20/08/2019 14:44
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