Epithelial Sodium Channels Are Activated by Furin-dependent Proteolysis

Rebecca P. Hughey, James B. Bruns, Carol L. Kinlough, Keri L. Harkleroad, Qiusheng Tong, Marcelo D. Carattino, John P. Johnson, James D. Stockand, Thomas R. Kleyman

Research output: Contribution to journalArticlepeer-review

335 Scopus citations


Epithelial Na+ channels (ENaCs) are activated by extracellular trypsin or by co-expression with channel-activating proteases, although there is no direct evidence that these proteases activate ENaC by cleaving the channel. We previously demonstrated that the α and γ subunits of ENaC are cleaved during maturation near consensus sites for furin cleavage. Using site-specific mutagenesis of channel subunits, ENaC expression in furin-deficient cells, and furin-specific inhibitors, we now report that ENaC cleavage correlates with channel activity. Channel activity in furin-deficient cells was rescued by expression of furin. Our data provide the first example of a vertebrate ion channel that is a substrate for furin and whose activity is dependent on its proteolysis.

Original languageEnglish (US)
Pages (from-to)18111-18114
Number of pages4
JournalJournal of Biological Chemistry
Issue number18
StatePublished - Apr 30 2004

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry
  • Cell Biology


Dive into the research topics of 'Epithelial Sodium Channels Are Activated by Furin-dependent Proteolysis'. Together they form a unique fingerprint.

Cite this