Journal
CELLULAR PHYSIOLOGY AND BIOCHEMISTRY
Volume 26, Issue 6, Pages 913-924Publisher
KARGER
DOI: 10.1159/000324000
Keywords
Ion channel regulation; Phosphorylation; Surface expression; Patch-clamp; Protein kinase B alpha; Serum- and glucocorticoid-inducible kinase isoform 1; Xenopus laevis oocytes
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Funding
- Deutsche Forschungsgemeinschaft [SFB 423]
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Kinases contribute to the regulation of the epithelial sodium channel (ENaC) in a complex manner. For example, SGK1 (serum-and glucocorticoid-inducible kinase type 1) enhances ENaC surface expression by phosphorylating Nedd4-2, thereby preventing ENaC retrieval and degradation. An additional mechanism of ENaC activation by SGK1 involves an SGK consensus motif ((RSRYWS621)-R-616) in the C-terminus of the channel's alpha-subunit. This consensus motif may also be a target for ENaC regulation by protein kinase B alpha (PKB alpha) known to be activated by insulin and growth factors. Therefore, we investigated a possible role of PKB alpha in the regulation of rat ENaC heterologously expressed in Xenopus laevis oocytes. We found that recombinant PKB alpha included in the pipette solution increased ENaC currents in outside-out patches by about 4-fold within 15-20 min. Replacing the serine residue S621 of the SGK consen-sus motif by an alanine (S621A) abolished this stimulatory effect. In co-expression experiments active PKB alpha but not catalytically inactive PKB alpha significantly increased ENaC whole-cell currents and surface expression by more than 50 % within 24 hours of co-expression. Interestingly, this stimulatory effect was preserved in oocytes expressing ENaC with the S621A mutation. We conclude that the acute stimulatory effect of PKB alpha involves a specific kinase consensus motif in the C-terminus of the channel's alpha-subunit. In contrast, the increase in channel surface expression caused by co-expression of PKB alpha does not depend on this site in the channel and is probably mediated by an effect on channel trafficking. Copyright (C) 2010 S. Karger AG, Basel
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