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Phosphorylation of Nedd4-2 by Sgk1 regulates epithelial Na(+) channel cell surface expression.

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  • 2001-12-18
Published in:
  • The EMBO journal. - 2001
Amino Acid Sequence
Animals
Calcium-Binding Proteins
Cell Line
Endosomal Sorting Complexes Required for Transport
Epithelial Sodium Channels
Immediate-Early Proteins
Ligases
Nedd4 Ubiquitin Protein Ligases
Nuclear Proteins
Oocytes
Phosphorylation
Protein Binding
Protein-Serine-Threonine Kinases
Sodium Channels
Ubiquitin
Ubiquitin-Protein Ligases
Xenopus Proteins
Xenopus laevis
English The epithelial Na(+) channel (ENaC) plays an essential role in the regulation of whole body Na(+) balance and blood pressure. The cell surface expression of this channel, a complex of three subunits (alpha, beta and gamma ENaC), has been shown to be regulated by hormones such as aldosterone and vasopressin and by intracellular signaling, including ubiquitylation and/or phosphorylation. However, the molecular mechanisms involving phosphorylation in the regulation of ENaC are unclear. Here we show by expression studies in Xenopus laevis oocytes that the aldosterone-induced Sgk1 kinase interacts with the ubiquitin protein ligase Nedd4-2 in a PY motif-dependent manner and phosphorylates Nedd4-2 on Ser444 and, to a lesser extent, Ser338. Such phosphorylation reduces the interaction between Nedd4-2 and ENaC, leading to elevated ENaC cell surface expression. These data show that phosphorylation of an enzyme involved in the ubiquitylation cascade (Nedd4-2) controls cell surface density of ENaC and propose a paradigm for the control of ion channels. Moreover, they suggest a novel and complete signaling cascade for aldosterone-dependent regulation of ENaC.
Language
  • English
Open access status
green
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Persistent URL
https://sonar.ch/global/documents/250874
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