Journal
MOLECULAR BIOLOGY OF THE CELL
Volume 18, Issue 11, Pages 4508-4518Publisher
AMER SOC CELL BIOLOGY
DOI: 10.1091/mbc.E06-08-0711
Keywords
-
Categories
Funding
- NIDDK NIH HHS [DK17433, R56 DK072614, DK072614, R01 DK072614, P01 DK017433] Funding Source: Medline
- NIMH NIH HHS [P01 MH040899, MH074866, P50 MH074866, MH40899] Funding Source: Medline
Ask authors/readers for more resources
The activity and trafficking of the Na+,K+-ATPase are regulated by several hormones, including dopamine, vasopressin, and adrenergic hormones through the action of G-protein-coupled receptors (GPCRs). Arrestins, GPCR kinases (GRKs), 14-3-3 proteins, and spinophilin interact with GPCRs and modulate the duration and magnitude of receptor signaling. We have found that arrestin 2 and 3, GRK 2 and 3,14-3-3 epsilon, and spinophilin directly associate with the Na+,K+-ATPase and that the associations with arrestins, GRKs, or 14-3-3 epsilon are blocked in the presence of spinophilin. In COS cells that overexpressed arrestin, the Na+,K+-ATPase was redistributed to intracellular compartments. This effect was not seen in mock-transfected cells or in cells expressing spinophilin. Furthermore, expression of spinophilin appeared to slow, whereas overexpression of beta-arrestins accelerated internalization of the Na+,K+-ATPase endocytosis. We also find that GRKs phosphorylate the Na+,K+-ATPase in vitro on its large cytoplasmic loop. Taken together, it appears that association with arrestins, GRKs, 14-3-3 epsilon, and spinophilin may be important modulators of Na+,K+-ATPase trafficking.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available