Phosphorylation and ubiquitination are necessary for Na,K-ATPase endocytosis during hypoxia

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• 作者：Laura A. Dada ; Lynn C. Welch ; Guofei Zhou ; Ronen Ben-Saadon ; Aaron Ciechanover ; Jacob I. Sznajder
• 关键词：Na ; K-ATPase ; Endocytosis ; Phosphorylation ; Ubiquitination ; Hypoxia
• 刊名：Cellular Signalling
• 出版年：2007
• 期刊代码：42_08986568
• 类别：bio
• 出版时间：September 2007
• 卷：19
• 期：9
• 页码：1893-1898
• 文件大小：577 K

摘要

As a cellular adaptative response, hypoxia decreases Na,K-ATPase activity by triggering the endocytosis of its α₁ 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 α₁ 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 α₁ 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 α₁-subunit endocytosis.