Proteolytic activation of the human epithelial sodium channel by trypsin IV and trypsin I involves distinct cleavage sites

Background: Proteolysis is required for ENaC activity, but the proteases activating ENaC in epithelial tissues are unknown. Results: Human trypsin IV and trypsin I activate ENaC by cleavage at distinct sites in the channel s -subunit. Conclusion: Cleavage at distinct sites may provide a mechanism for differential ENaC regulation by tissue-specific proteases. Significance: ENaC activation by trypsin IV may contribute to ENaC regulation in vivo.