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J Biol Chem
2008 Dec 26;28352:36586-91. doi: 10.1074/jbc.M805676200.
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Plasmin activates epithelial Na+ channels by cleaving the gamma subunit.
Passero CJ
,
Mueller GM
,
Rondon-Berrios H
,
Tofovic SP
,
Hughey RP
,
Kleyman TR
.
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Proteolytic processing of epithelial sodium channel (ENaC) subunits occurs as channels mature within the biosynthetic pathway. The proteolytic processing events of the alpha and gamma subunits are associated with channel activation. Furin cleaves the alpha subunit ectodomain at two sites, releasing an inhibitory tract and activating the channel. However, furin cleaves the gamma subunit ectodomain only once. A second distalcleavage in the gamma subunit induced by other proteases, such as prostasin and elastase, is required to release a second inhibitory tract and further activate the channel. We found that the serine protease plasmin activates ENaC in association with inducing cleavage of the gamma subunit at gammaLys194, a site distal to the furin site. A gammaK194A mutant prevented both plasmin-dependent activation of ENaC and plasmin-dependent production of a unique 70-kDa carboxyl-terminal gamma subunit cleavage fragment. Plasmin-dependent cleavage and activation of ENaC may have a role in extracellular volume expansion in human disorders associated with proteinuria, as filtered plasminogen may be processed by urokinase, released from renal tubular epithelium, to generate active plasmin.
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,
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Neutrophil elastase activates near-silent epithelial Na+ channels and increases airway epithelial Na+ transport.
2005,
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Caldwell,
Serine protease activation of near-silent epithelial Na+ channels.
2004,
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Carattino,
Arachidonic acid regulates surface expression of epithelial sodium channels.
2003,
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,
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Carattino,
The epithelial Na+ channel is inhibited by a peptide derived from proteolytic processing of its alpha subunit.
2006,
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,
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Carattino,
Defining an inhibitory domain in the alpha-subunit of the epithelial sodium channel.
2008,
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,
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Chraïbi,
Protease modulation of the activity of the epithelial sodium channel expressed in Xenopus oocytes.
1998,
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,
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Gosalia,
Profiling serine protease substrate specificity with solution phase fluorogenic peptide microarrays.
2005,
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Harris,
A novel neutrophil elastase inhibitor prevents elastase activation and surface cleavage of the epithelial sodium channel expressed in Xenopus laevis oocytes.
2007,
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,
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Hughey,
Role of proteolysis in the activation of epithelial sodium channels.
2007,
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Hughey,
Epithelial sodium channels are activated by furin-dependent proteolysis.
2004,
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,
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Hughey,
Distinct pools of epithelial sodium channels are expressed at the plasma membrane.
2004,
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,
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Hughey,
Maturation of the epithelial Na+ channel involves proteolytic processing of the alpha- and gamma-subunits.
2003,
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,
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Kim,
Increased apical targeting of renal ENaC subunits and decreased expression of 11betaHSD2 in HgCl2-induced nephrotic syndrome in rats.
2006,
Pubmed
Kim,
Pathogenesis of oedema in nephrotic syndrome: role of epithelial sodium channel.
2007,
Pubmed
Kleyman,
Regulation of ENaCs by proteases: An increasingly complex story.
2006,
Pubmed
,
Xenbase
Kristensen,
Localization of urokinase-type plasminogen activator messenger RNA in the normal mouse by in situ hybridization.
1991,
Pubmed
Lau,
Plasminogen and antithrombin III deficiencies in the childhood nephrotic syndrome associated with plasminogenuria and antithrombinuria.
1980,
Pubmed
Picard,
Defective ENaC processing and function in tissue kallikrein-deficient mice.
2008,
Pubmed
Piedagnel,
Urokinase (u-PA) is produced by collecting duct principal cells and is post-transcriptionally regulated by SV40 large-T, arginine vasopressin, and epidermal growth factor.
2006,
Pubmed
Rafikova,
Renal and metabolic effects of tempol in obese ZSF1 rats--distinct role for superoxide and hydrogen peroxide in diabetic renal injury.
2008,
Pubmed
Sheng,
Characterization of the selectivity filter of the epithelial sodium channel.
2000,
Pubmed
,
Xenbase
Sheng,
Furin cleavage activates the epithelial Na+ channel by relieving Na+ self-inhibition.
2006,
Pubmed
,
Xenbase
Svenningsen,
Plasmin in nephrotic urine activates the epithelial sodium channel.
2009,
Pubmed
,
Xenbase
Syrovets,
Novel aspects and new roles for the serine protease plasmin.
2004,
Pubmed
TROLL,
The action of plasmin on synthetic substrates.
1954,
Pubmed
Vallet,
An epithelial serine protease activates the amiloride-sensitive sodium channel.
1997,
Pubmed
,
Xenbase
Vaziri,
Plasma levels and urinary excretion of fibrinolytic and protease inhibitory proteins in nephrotic syndrome.
1994,
Pubmed
Wagner,
Sites of urokinase-type plasminogen activator expression and distribution of its receptor in the normal human kidney.
1996,
Pubmed
