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The kinase Grk2 regulates Nedd4/Nedd4-2-dependent control of epithelial Na+ channels.

Publication ,  Journal Article
Dinudom, A; Fotia, AB; Lefkowitz, RJ; Young, JA; Kumar, S; Cook, DI
Published in: Proc Natl Acad Sci U S A
August 10, 2004

Epithelial Na(+) channels mediate the transport of Na across epithelia in the kidney, gut, and lungs and are required for blood pressure regulation. They are inhibited by ubiquitin protein ligases, such as Nedd4 and Nedd4-2, with loss of this inhibition leading to hypertension. Here, we report that these channels are maintained in the active state by the G protein-coupled receptor kinase, Grk2, which has been previously implicated in the development of essential hypertension. We also show that Grk2 phosphorylates the C terminus of the channel beta subunit and renders the channels insensitive to inhibition by Nedd4-2. This mechanism has not been previously reported to regulate epithelial Na(+) channels and provides a potential explanation for the observed association of Grk2 overactivity with hypertension. Here, we report a G protein-coupled receptor kinase regulating a membrane protein other than a receptor and provide a paradigm for understanding how the interaction between membrane proteins and ubiquitin protein ligases is controlled.

Duke Scholars

Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

August 10, 2004

Volume

101

Issue

32

Start / End Page

11886 / 11890

Location

United States

Related Subject Headings

  • beta-Adrenergic Receptor Kinases
  • Ubiquitin-Protein Ligases
  • Sodium Channels
  • Sodium Channel Agonists
  • Salivary Ducts
  • Receptors, G-Protein-Coupled
  • Phosphorylation
  • Nedd4 Ubiquitin Protein Ligases
  • Models, Chemical
  • Mice
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Dinudom, A., Fotia, A. B., Lefkowitz, R. J., Young, J. A., Kumar, S., & Cook, D. I. (2004). The kinase Grk2 regulates Nedd4/Nedd4-2-dependent control of epithelial Na+ channels. Proc Natl Acad Sci U S A, 101(32), 11886–11890. https://doi.org/10.1073/pnas.0402178101
Dinudom, Anuwat, Andrew B. Fotia, Robert J. Lefkowitz, John A. Young, Sharad Kumar, and David I. Cook. “The kinase Grk2 regulates Nedd4/Nedd4-2-dependent control of epithelial Na+ channels.Proc Natl Acad Sci U S A 101, no. 32 (August 10, 2004): 11886–90. https://doi.org/10.1073/pnas.0402178101.
Dinudom A, Fotia AB, Lefkowitz RJ, Young JA, Kumar S, Cook DI. The kinase Grk2 regulates Nedd4/Nedd4-2-dependent control of epithelial Na+ channels. Proc Natl Acad Sci U S A. 2004 Aug 10;101(32):11886–90.
Dinudom, Anuwat, et al. “The kinase Grk2 regulates Nedd4/Nedd4-2-dependent control of epithelial Na+ channels.Proc Natl Acad Sci U S A, vol. 101, no. 32, Aug. 2004, pp. 11886–90. Pubmed, doi:10.1073/pnas.0402178101.
Dinudom A, Fotia AB, Lefkowitz RJ, Young JA, Kumar S, Cook DI. The kinase Grk2 regulates Nedd4/Nedd4-2-dependent control of epithelial Na+ channels. Proc Natl Acad Sci U S A. 2004 Aug 10;101(32):11886–11890.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

August 10, 2004

Volume

101

Issue

32

Start / End Page

11886 / 11890

Location

United States

Related Subject Headings

  • beta-Adrenergic Receptor Kinases
  • Ubiquitin-Protein Ligases
  • Sodium Channels
  • Sodium Channel Agonists
  • Salivary Ducts
  • Receptors, G-Protein-Coupled
  • Phosphorylation
  • Nedd4 Ubiquitin Protein Ligases
  • Models, Chemical
  • Mice