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Type: Journal article
Title: The kinase Grk2 regulates Nedd4/Nedd4-2-dependent control of epithelial Na+ channels
Author: Dinudom, A.
Fotia, A.
Lefkowitz, R.
Young, J.
Kumar, S.
Cook, D.
Citation: Proceedings of the National Academy of Sciences of USA, 2004; 101(32):11886-11890
Publisher: Natl Acad Sciences
Issue Date: 2004
ISSN: 0027-8424
Statement of
Anuwat Dinudom, Andrew B. Fotia, Robert J. Lefkowitz, John A. Young, Sharad Kumar, and David I. Cook
Abstract: 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.
Keywords: Salivary Ducts
Cells, Cultured
Epithelial Cells
Ubiquitin-Protein Ligases
Cyclic AMP-Dependent Protein Kinases
Sodium Channels
Receptors, G-Protein-Coupled
Models, Chemical
beta-Adrenergic Receptor Kinases
Feedback, Physiological
Endosomal Sorting Complexes Required for Transport
Sodium Channel Agonists
Nedd4 Ubiquitin Protein Ligases
DOI: 10.1073/pnas.0402178101
Appears in Collections:Aurora harvest
Medicine publications

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