Journal article
Kinase regulation of hENaC mediated through a region in the COOH-terminal portion of the α-subunit
American Journal of Physiology: Cell Physiology, Vol.278(5), pp.C1047-C1054
05/01/2000
DOI: 10.1152/ajpcell.2000.278.5.C1047
PMID: 10794679
Abstract
In an effort to gain insight into how kinases might regulate epithelial Na+ channel (ENaC) activity, we expressed human ENaC (hENaC) in Xenopus oocytes and examined the effect of agents that modulate the activity of some kinases. Activation of protein kinase C (PKC) by phorbol ester increased the activity of ENaC, but only in oocytes with a baseline current of <2,000 nA. Inhibitors of protein kinases produced varying effects. Chelerythrine, an inhibitor of PKC, produced a significant inhibition of ENaC current, but calphostin C, another PKC inhibitor, had no effect. The PKA/protein kinase G inhibitor H-8 had no effect, whereas the p38 mitogen-activated protein kinase inhibitor, SB-203580 had a significant inhibitory effect. Staurosporine, a nonspecific kinase inhibitor, was the most potent tested. It inhibited ENaC currents in both oocytes and in M-1 cells, a model for the collecting duct. Site-directed mutagenesis revealed that the staurosporine effect did not require an intact COOH terminus of either the β- or γ-hENaC subunit. However, an intact COOH terminus of the α-subunit was required for this effect. These results suggest that an integrated kinase network regulates ENaC activity through an action that requires a portion of the α-subunit.
Details
- Title: Subtitle
- Kinase regulation of hENaC mediated through a region in the COOH-terminal portion of the α-subunit
- Creators
- Kenneth A Volk - Department of Internal Medicine, University of Iowa and Department of Veterans Affairs Medical Center, Iowa City, Iowa 52242Russell F Husted - Department of Internal Medicine, University of Iowa and Department of Veterans Affairs Medical Center, Iowa City, Iowa 52242Peter M Snyder - Department of Internal Medicine, University of Iowa and Department of Veterans Affairs Medical Center, Iowa City, Iowa 52242John B Stokes - Department of Internal Medicine, University of Iowa and Department of Veterans Affairs Medical Center, Iowa City, Iowa 52242
- Resource Type
- Journal article
- Publication Details
- American Journal of Physiology: Cell Physiology, Vol.278(5), pp.C1047-C1054
- DOI
- 10.1152/ajpcell.2000.278.5.C1047
- PMID
- 10794679
- ISSN
- 0363-6143
- eISSN
- 1522-1563
- Language
- English
- Date published
- 05/01/2000
- Academic Unit
- Molecular Physiology and Biophysics; Cardiovascular Medicine; Medicine Administration; Internal Medicine
- Record Identifier
- 9984025433602771
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