Regulation of Epithelial Sodium Channel Activity through a Region of the Carboxyl Terminus of the α-Subunit: EVIDENCE FOR INTRACELLULAR KINASE-MEDIATED REACTIONS

Kenneth A Volk; Peter M Snyder; John B Stokes

doi:10.1074/jbc.M108714200

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Regulation of Epithelial Sodium Channel Activity through a Region of the Carboxyl Terminus of the α-Subunit: EVIDENCE FOR INTRACELLULAR KINASE-MEDIATED REACTIONS

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Regulation of Epithelial Sodium Channel Activity through a Region of the Carboxyl Terminus of the α-Subunit: EVIDENCE FOR INTRACELLULAR KINASE-MEDIATED REACTIONS

Kenneth A Volk, Peter M Snyder and John B Stokes

The Journal of biological chemistry, Vol.276(47), pp.43887-43893

11/23/2001

DOI: 10.1074/jbc.M108714200

PMID: 11571309

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Abstract

The epithelial sodium channel (ENaC) is a heteromultimer composed of three subunits, each having two membrane-spanning domains with intracellular amino and carboxyl termini. Several hormones and proteins regulate channel activity, but the molecular nature of this regulation is unknown. We conducted experiments to determine a possible new site within the carboxyl terminus of the alpha-subunit involved in enhanced channel activity through endogenous kinases. When an alpha-subunit that was truncated to remove a PY motif was expressed in Xenopus oocytes with wild type human beta- and gamma-ENaC subunits, channel activity was greatly enhanced. The removal of the entire intracellular carboxyl terminus of the alpha-subunit eliminated this enhanced basal activity. Using several point mutations, we localized this site to two amino acid residues (Pro(595)-Gly(596)) near the second membrane-spanning domain. The nonspecific kinase inhibitor staurosporine inhibits basal channel activity of wild type ENaC but was ineffective in inhibiting channels mutated at this site. The major effect of these mutations was not on channel kinetics but was largely, if not entirely, on the number of active channels on the cell surface. This region is potentially important in effecting kinase-mediated increases in ENaC activity.

Details

Title: Subtitle: Regulation of Epithelial Sodium Channel Activity through a Region of the Carboxyl Terminus of the α-Subunit: EVIDENCE FOR INTRACELLULAR KINASE-MEDIATED REACTIONS
Creators: Kenneth A Volk
Peter M Snyder
John B Stokes
Resource Type: Journal article
Publication Details: The Journal of biological chemistry, Vol.276(47), pp.43887-43893
DOI: 10.1074/jbc.M108714200
PMID: 11571309
NLM abbreviation: J Biol Chem
ISSN: 0021-9258
eISSN: 1083-351X
Language: English
Date published: 11/23/2001
Academic Unit: Molecular Physiology and Biophysics; Cardiovascular Medicine; Medicine Administration; Internal Medicine
Record Identifier: 9984025598602771

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