Linked Life Data

20630937

Source:http://linkedlifedata.com/resource/pubmed/id/20630937

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2010-10-4
pubmed:abstractText
Proteases activate the epithelial sodium channel (ENaC) by cleaving the large extracellular domains of the ?- and ?-subunits and releasing peptides with inhibitory properties. Furin and prostasin activate mouse ENaC by cleaving the ?-subunit at sites flanking a 43 residue inhibitory tract (?E144-K186). To determine whether there is a minimal inhibitory region within this 43 residue tract, we generated serial deletions in the inhibitory tract of the ?-subunit in channels resistant to cleavage by furin and prostasin. We found that partial or complete deletion of a short segment in the ?-subunit, R158-N171, enhanced channel activity. Synthetic peptides overlapping this segment in the ?-subunit further identified a key 11-mer tract, R158-F168 (RFLNLIPLLVF), which inhibited wild-type ENaC expressed in Xenopus laevis oocytes, and endogenous channels in mpkCCD cells and human airway epithelia. Further studies with amino acid-substituted peptides defined residues that are required for inhibition in this key 11-mer tract. The presence of the native ? inhibitory tract in ENaC weakened the intrinsic binding constant of the 11-mer peptide inhibitor, suggesting that the ? inhibitory tract and the 11-mer peptide interact at overlapping sites within the channel.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1522-1466
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
299
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
F854-61
pubmed:dateRevised
2011-10-3
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Defining an inhibitory domain in the gamma subunit of the epithelial sodium channel.
pubmed:affiliation
Renal Electrolyte Div., Dept. of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural