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Na,K-ATPase alpha1-subunit dephosphorylation by protein phosphatase 2A is necessary for its recruitment to the plasma membrane.
- Source :
-
FASEB journal : official publication of the Federation of American Societies for Experimental Biology [FASEB J] 2006 Dec; Vol. 20 (14), pp. 2618-20. Date of Electronic Publication: 2006 Oct 25. - Publication Year :
- 2006
-
Abstract
- In alveolar epithelial cells, G-protein coupled-receptors agonists (GPCR) induce the recruitment of the Na,K-ATPase to the plasma membrane. Here we report that for the recruitment of the Na,K-ATPase to occur, dephosphorylation of its alpha1-subunit at serine 18 is necessary, as demonstrated by in vitro phosphorylation, mutation of the serine 18 to alanine, and use of a specific phospho-antibody. Several approaches strongly suggest dephosphorylation to be mediated by protein phosphatase 2A (PP2A): 1) Na,K-ATPase dephosphorylation and recruitment were prevented by okadaic acid (OA); 2) the Na,K-ATPase alpha1-subunit is an in vitro substrate for PP2A; and 3) glutathione S-transferase (GST)-fusion proteins binding assays demonstrate a direct interaction between the catalytic subunit of PP2A and the first 90 amino acids of the Na,K-ATPase alpha1-subunit. Finally, GPCR agonists induced a rapid translocation of PP2A from the cytosol to the membrane fraction, which corresponded with increased coimmunoprecipitation and colocalization of PP2A and the Na,K-ATPase. Accordingly, we provide evidence that GPCR agonists promote PP2A translocation to the membrane fraction, leading to the dephosphorylation of the Na,K-ATPase alpha1-subunit at the serine 18 residue and its recruitment to the cell plasma membrane, which is of biological and physiological importance.
- Subjects :
- Amino Acid Sequence
Animals
Cell Line
Epithelial Cells metabolism
Humans
Male
Protein Phosphatase 2
Protein Subunits
Protein Transport physiology
Rats
Rats, Sprague-Dawley
Receptors, G-Protein-Coupled agonists
Phosphoprotein Phosphatases metabolism
Sodium-Potassium-Exchanging ATPase metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1530-6860
- Volume :
- 20
- Issue :
- 14
- Database :
- MEDLINE
- Journal :
- FASEB journal : official publication of the Federation of American Societies for Experimental Biology
- Publication Type :
- Academic Journal
- Accession number :
- 17065225
- Full Text :
- https://doi.org/10.1096/fj.06-6503fje