期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 282, 期 9, 页码 6153-6160出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M610636200
关键词
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资金
- NIDDK NIH HHS [P30 DK072506, P50 DK54690, DK065161] Funding Source: Medline
Epithelial sodium channels (ENaC) are expressed in the apical membrane of high resistance Na+ transporting epithelia and have a key role in regulating extracellular fluid volume and the volume of airway surface liquids. Maturation and activation of ENaC subunits involves furin-dependent cleavage of the ectodomain at two sites in the alpha subunit and at a single site within the gamma subunit. We now report that the serine protease prostasin further activates ENaC by inducing cleavage of the gamma subunit at a site distal to the furin cleavage site. Dual cleavage of the gamma subunit is predicted to release a 43-amino acid peptide. Channels with a gamma subunit lacking this 43-residue tract have increased activity due to a high open probability. A synthetic peptide corresponding to the fragment cleaved from the gamma subunit is a reversible inhibitor of endogenous ENaCs in mouse corticalcollecting duct cells and in primary cultures of human airway epithelial cells. Our results suggest that multiple proteases cleave ENaC gamma subunits to fully activate the channel.
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