PMID- 10473631
OWN - NLM
STAT- MEDLINE
DCOM- 19991018
LR  - 20191210
IS  - 1059-1524 (Print)
IS  - 1059-1524 (Linking)
VI  - 10
IP  - 9
DP  - 1999 Sep
TI  - Insulin-induced stimulation of Na+,K(+)-ATPase activity in kidney proximal tubule
      cells depends on phosphorylation of the alpha-subunit at Tyr-10.
PG  - 2847-59
AB  - 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.
FAU - Feraille, E
AU  - Feraille E
AD  - Division de Nephrologie, Fondation pour Recherches Medicales, 1211 Geneve 4,
      Switzerland. feraille@cmu.unige.ch
FAU - Carranza, M L
AU  - Carranza ML
FAU - Gonin, S
AU  - Gonin S
FAU - Beguin, P
AU  - Beguin P
FAU - Pedemonte, C
AU  - Pedemonte C
FAU - Rousselot, M
AU  - Rousselot M
FAU - Caverzasio, J
AU  - Caverzasio J
FAU - Geering, K
AU  - Geering K
FAU - Martin, P Y
AU  - Martin PY
FAU - Favre, H
AU  - Favre H
LA  - eng
GR  - R01DK53460/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Mol Biol Cell
JT  - Molecular biology of the cell
JID - 9201390
RN  - 0 (Insulin)
RN  - 0 (Insulin Antagonists)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 21820-51-9 (Phosphotyrosine)
RN  - 3WHH0066W5 (Vanadates)
RN  - 42HK56048U (Tyrosine)
RN  - 5ACL011P69 (Ouabain)
RN  - DH2M523P0H (Genistein)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 7.2.2.13 (Sodium-Potassium-Exchanging ATPase)
SB  - IM
MH  - Amino Acid Substitution
MH  - Animals
MH  - Cells, Cultured
MH  - Enzyme Activation/drug effects
MH  - Genistein/pharmacology
MH  - Insulin/*pharmacology
MH  - Insulin Antagonists/pharmacology
MH  - Kidney Tubules, Proximal/cytology/drug effects/*enzymology
MH  - Male
MH  - Opossums
MH  - Ouabain/pharmacology
MH  - Phosphorylation/drug effects
MH  - Phosphotyrosine/*metabolism
MH  - Protein Kinase Inhibitors
MH  - Protein Kinases/metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Sodium-Potassium-Exchanging ATPase/antagonists & inhibitors/chemistry/*metabolism
MH  - Transfection
MH  - Tyrosine/genetics/metabolism
MH  - Vanadates/pharmacology
PMC - PMC25522
EDAT- 1999/09/03 00:00
MHDA- 1999/09/03 00:01
CRDT- 1999/09/03 00:00
PHST- 1999/09/03 00:00 [pubmed]
PHST- 1999/09/03 00:01 [medline]
PHST- 1999/09/03 00:00 [entrez]
AID - 10.1091/mbc.10.9.2847 [doi]
PST - ppublish
SO  - Mol Biol Cell. 1999 Sep;10(9):2847-59. doi: 10.1091/mbc.10.9.2847.