期刊
CELLULAR SIGNALLING
卷 19, 期 9, 页码 1893-1898出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.cellsig.2007.04.013
关键词
Na,K-ATPase; endocytosis; phosphorylation; ubiquitination; hypoxia
类别
资金
- NHLBI NIH HHS [HL-P01-71643, P01 HL071643-050001, P01 HL071643] Funding Source: Medline
As a cellular adaptative response, hypoxia decreases Na,K-ATPase activity by triggering the endocytosis of its alpha(1) subunit in alveolar epithelial cells. Here, we present evidence that the ubiquitin conjugating system is important in the Na,K-ATPase endocytosis during hypoxia and that ubiquitination of Na,K-ATPase alpha(1) subunit occurs at the basolateral membrane. Endocytosis and ubiquitination were prevented when the Ser 18 in the PKC phosphorylation motif of the Na,K-ATPase alpha(1) subunit was mutated to an alanine, suggesting that phosphorylation at Ser-18 is required for ubiquitination. Mutation of the four lysines surrounding Ser 18 to arginine prevented Na,K-ATPase ubiquitination and endocytosis during hypoxia; however, only one of them was sufficient to restore hypoxia-induced endocytosis. We provide evidence that ubiquitination plays an important role in cellular adaptation to hypoxia by regulating Na,K-ATPase alpha(1)-subunit endocytosis. (c) 2007 Elsevier Inc. All rights reserved.
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