PubMed 15358127

Referenced in Channelpedia wiki pages of: none

Automatically associated channels: ClvC2 , ClvC4

Title: Serum and glucocorticoid inducible kinases functionally regulate ClC-2 channels.

Authors: Monica Palmada, Michael Dieter, Christoph Boehmer, Siegfried Waldegger, Florian Lang

Journal, date & volume: Biochem. Biophys. Res. Commun., 2004 Sep 3 , 321, 1001-6

PubMed link:

ClC-2 participates in the regulation of neuronal excitability, chloride secretion, and cell volume. The ClC-2 sequence contains a consensus site (Ser82) for phosphorylation by the serum and glucocorticoid inducible kinase isoforms SGK1-3. Thus, the present study explored whether ClC-2 is regulated by those kinases. ClC-2 expression in Xenopus oocytes induced inwardly rectifying currents that increased upon coexpression of SGK1-3 and the related kinase PKB. The stimulatory effect was still present upon disruption of the SGK phosphorylation site. SGKs can phosphorylate the ubiquitin ligase Nedd4-2 and prevent Nedd4-2 from binding to its target. Therefore, the role of Nedd4-2 in ClC-2 modulation was investigated. ClC-2 activity decreased upon Nedd4-2 coexpression, an effect reversed by the kinases. According to chemiluminescence ClC-2 membrane abundance was enhanced by SGKs and diminished by Nedd4-2. These observations suggest that SGK1-3 and Nedd4-2 regulate ClC-2 at least in part by modulating ClC-2 abundance at the plasma membrane.