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Vol. 26, No. 6, 2010
Issue release date: 2010
Cell Physiol Biochem 2010;26:913–924
(DOI:10.1159/000324000)
Original Paper

Protein Kinase B Alpha (PKBα) Stimulates the Epithelial Sodium Channel (ENaC) Heterologously Expressed in Xenopus laevis Oocytes by Two Distinct Mechanisms

Diakov A. · Nesterov V. · Mokrushina M. · Rauh R. · Korbmacher C.
Institut für Zelluläre und Molekulare Physiologie, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen

Abstract

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 (616RSRYWS621) in the C-terminus of the channel’s α-subunit. This consensus motif may also be a target for ENaC regulation by protein kinase B α (PKBα) known to be activated by insulin and growth factors. Therefore, we investigated a possible role of PKBα in the regulation of rat ENaC heterologously expressed in Xenopus laevis oocytes. We found that recombinant PKBα 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 consensus motif by an alanine (S621A) abolished this stimulatory effect. In co-expression experiments active PKBα but not catalytically inactive PKBα 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 PKBα involves a specific kinase consensus motif in the C-terminus of the channel’s α-subunit. In contrast, the increase in channel surface expression caused by co-expression of PKBα does not depend on this site in the channel and is probably mediated by an effect on channel trafficking.

 goto top of outline Author Contacts

Prof. Dr. med. Christoph Korbmacher
Institut für Zelluläre und Molekulare Physiologie
Waldstr. 6, 91054 Erlangen (Germany)
Tel. +49-9131-8522301, Fax +49-9131-8522770
E-Mail christoph.korbmacher@physiologie2.med.uni-erlangen.de


 goto top of outline Article Information

Accepted: October 13, 2010
Published online: January 04, 2011
Number of Print Pages : 12


 goto top of outline Publication Details

Cellular Physiology and Biochemistry (International Journal of Experimental Cellular Physiology, Biochemistry andPharmacology)

Vol. 26, No. 6, Year 2010 (Cover Date: 2010)

Journal Editor: F. Lang, Tübingen
ISSN: 1015–8987 (Print), eISSN: 1421–9778 (Online)

For additional information: http://www.karger.com/journals/cpb


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