Phosphorylation-dependent binding of 14-3-3 proteins controls TRESK regulation

Research output: Contribution to journalArticle

39 Citations (Scopus)


The two-pore domain K+ channel, TRESK (TWIK-related spinal cord K+ channel) is reversibly activated by the calcium/calmodulin- dependent protein phosphatase, calcineurin. In the present study, we report that 14-3-3 proteins directly bind to the intracellular loop of TRESK and control the kinetics of the calcium-dependent regulation of the channel. Coexpression of 14-3-3η with TRESK blocked, whereas the coexpression of a dominant negative form of 14-3-3η accelerated the return of the K+ current to the resting state after the activation mediated by calcineurin in Xenopus oocytes. The direct action of 14-3-3 was spatially restricted to TRESK, since 14-3-3η was also effective, when it was tethered to the channel by a flexible polyglutamine-containing chain. The effect of both the coexpressed and chained 14-3-3 was alleviated by the microinjection of Ser(P)-Raf259 phosphopeptide that competes with TRESK for binding to 14-3-3. The γ and η isoforms of 14-3-3 controlled TRESK regulation, whereas the β, ζ, ε-, σ, and τ isoforms failed to influence the mechanism significantly. Phosphorylation of serine 264 in mouse TRESK was required for the binding of 14-3-3η. Because 14-3-3 proteins are ubiquitous, they are expected to control the duration of calcineurin-mediated TRESK activation in all the cell types that express the channel, depending on the phosphorylation state of serine 264. This kind of direct control of channel regulation by 14-3-3 is unique within the two-pore domain K+ channel family.

Original languageEnglish
Pages (from-to)15672-15680
Number of pages9
JournalJournal of Biological Chemistry
Issue number23
Publication statusPublished - Jun 6 2008

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Phosphorylation-dependent binding of 14-3-3 proteins controls TRESK regulation'. Together they form a unique fingerprint.

  • Cite this