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J Biol Chem
2006 Jun 02;28122:15194-200. doi: 10.1074/jbc.M513809200.
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Modulation of voltage-dependent Shaker family potassium channels by an aldo-keto reductase.
Weng J
,
Cao Y
,
Moss N
,
Zhou M
.
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The beta subunit (Kvbeta) of the Shaker family voltage-dependent potassium channels (Kv1) is a cytosolic protein that forms a permanent complex with the channel. Sequence and structural conservation indicates that Kvbeta resembles an aldo-keto reductase (AKR), an enzyme that catalyzes a redox reaction using an NADPH cofactor. A putative AKR in complex with a Kv channel has led to the hypothesis that intracellular redox potential may dynamically influence the excitability of a cell through Kvbeta. Since the AKR function of Kvbeta has never been demonstrated, a direct functional coupling between the two has not been established. We report here the identification of Kvbeta substrates and the demonstration that Kvbeta is a functional AKR. We have also found that channel function is modulated when the Kvbeta-bound NADPH is oxidized. Further studies of the enzymatic properties of Kvbeta seem to favor the role of Kvbeta as a redox sensor. These results suggest that Kvbeta may couple the excitability of the cell to its metabolic state and present a new avenue of research that may lead to understanding of the physiological functions of Kvbeta.
Accili,
Separable Kvbeta subunit domains alter expression and gating of potassium channels.
1997, Pubmed,
Xenbase
Accili,
Separable Kvbeta subunit domains alter expression and gating of potassium channels.
1997,
Pubmed
,
Xenbase
Accili,
Separable effects of human Kvbeta1.2 N- and C-termini on inactivation and expression of human Kv1.4.
1998,
Pubmed
,
Xenbase
Askonas,
The kinetic mechanism catalysed by homogeneous rat liver 3 alpha-hydroxysteroid dehydrogenase. Evidence for binary and ternary dead-end complexes containing non-steroidal anti-inflammatory drugs.
1991,
Pubmed
Barski,
Mechanism of human aldehyde reductase: characterization of the active site pocket.
1995,
Pubmed
Castellino,
Time- and voltage-dependent modulation of a Kv1.4 channel by a beta-subunit (Kv beta 3) cloned from ferret ventricle.
1995,
Pubmed
,
Xenbase
Coppock,
Molecular basis of hypoxia-induced pulmonary vasoconstriction: role of voltage-gated K+ channels.
2001,
Pubmed
Grimshaw,
Kinetic and structural effects of activation of bovine kidney aldose reductase.
1989,
Pubmed
Gulbis,
Structure of the cytoplasmic beta subunit-T1 assembly of voltage-dependent K+ channels.
2000,
Pubmed
,
Xenbase
Gulbis,
Structure of a voltage-dependent K+ channel beta subunit.
1999,
Pubmed
Haddad,
Different O2-sensing mechanisms by different K+ channels.
2000,
Pubmed
Haddad,
O2-sensing mechanisms in excitable cells: role of plasma membrane K+ channels.
1997,
Pubmed
Heinemann,
Molecular and functional characterization of a rat brain Kv beta 3 potassium channel subunit.
1995,
Pubmed
,
Xenbase
Heinemann,
Functional characterization of Kv channel beta-subunits from rat brain.
1996,
Pubmed
,
Xenbase
Heredia,
Dissection of the physiological interconversion of 5alpha-DHT and 3alpha-diol by rat 3alpha-HSD via transient kinetics shows that the chemical step is rate-determining: effect of mutating cofactor and substrate-binding pocket residues on catalysis.
2004,
Pubmed
Hoshi,
Biophysical and molecular mechanisms of Shaker potassium channel inactivation.
1990,
Pubmed
,
Xenbase
Hyndman,
The aldo-keto reductase superfamily homepage.
2003,
Pubmed
Jez,
Characterization of the substrate binding site in rat liver 3alpha-hydroxysteroid/dihydrodiol dehydrogenase. The roles of tryptophans in ligand binding and protein fluorescence.
1996,
Pubmed
Jez,
Comparative anatomy of the aldo-keto reductase superfamily.
1997,
Pubmed
Kubiseski,
Studies on pig muscle aldose reductase. Kinetic mechanism and evidence for a slow conformational change upon coenzyme binding.
1992,
Pubmed
Lee,
Characterization of 4-oxo-2-nonenal as a novel product of lipid peroxidation.
2000,
Pubmed
Liu,
Binding of pyridine nucleotide coenzymes to the beta-subunit of the voltage-sensitive K+ channel.
2001,
Pubmed
Liu,
Oxidative stress and potassium channel function.
2002,
Pubmed
Long,
Crystal structure of a mammalian voltage-dependent Shaker family K+ channel.
2005,
Pubmed
McCormack,
Shaker K+ channel beta subunits belong to an NAD(P)H-dependent oxidoreductase superfamily.
1994,
Pubmed
Morales,
A novel beta subunit increases rate of inactivation of specific voltage-gated potassium channel alpha subunits.
1995,
Pubmed
,
Xenbase
Parcej,
Oligomeric properties of alpha-dendrotoxin-sensitive potassium ion channels purified from bovine brain.
1992,
Pubmed
Pardo,
Extracellular K+ specifically modulates a rat brain K+ channel.
1992,
Pubmed
,
Xenbase
Patel,
Molecular physiology of oxygen-sensitive potassium channels.
2001,
Pubmed
Penning,
Engineering steroid hormone specificity into aldo-keto reductases.
2001,
Pubmed
Rasmusson,
C-type inactivation controls recovery in a fast inactivating cardiac K+ channel (Kv1.4) expressed in Xenopus oocytes.
1995,
Pubmed
,
Xenbase
Rettig,
Inactivation properties of voltage-gated K+ channels altered by presence of beta-subunit.
1994,
Pubmed
,
Xenbase
Rindgen,
Covalent modifications to 2'-deoxyguanosine by 4-oxo-2-nonenal, a novel product of lipid peroxidation.
1999,
Pubmed
Rozanski,
A metabolic mechanism for cardiac K+ channel remodelling.
2002,
Pubmed
Ruppersberg,
Regulation of fast inactivation of cloned mammalian IK(A) channels by cysteine oxidation.
1991,
Pubmed
,
Xenbase
Schlegel,
Mutagenesis of 3 alpha-hydroxysteroid dehydrogenase reveals a "push-pull" mechanism for proton transfer in aldo-keto reductases.
1998,
Pubmed
Schultz,
Localization of two potassium channel beta subunit genes, KCNA1B and KCNA2B.
1996,
Pubmed
Scott,
Primary structure of a beta subunit of alpha-dendrotoxin-sensitive K+ channels from bovine brain.
1994,
Pubmed
Sewing,
Kv beta 1 subunit binding specific for shaker-related potassium channel alpha subunits.
1996,
Pubmed
Shi,
Beta subunits promote K+ channel surface expression through effects early in biosynthesis.
1996,
Pubmed
Tarle,
Probing the active site of human aldose reductase. Site-directed mutagenesis of Asp-43, Tyr-48, Lys-77, and His-110.
1993,
Pubmed
Tseng-Crank,
Functional role of the NH2-terminal cytoplasmic domain of a mammalian A-type K channel.
1993,
Pubmed
,
Xenbase
Weir,
Acute oxygen-sensing mechanisms.
2005,
Pubmed
Yu,
NAB domain is essential for the subunit assembly of both alpha-alpha and alpha-beta complexes of shaker-like potassium channels.
1996,
Pubmed
