Alternative splicing switches potassium channel sensitivity to protein phosphorylation.

نویسندگان

  • L Tian
  • R R Duncan
  • M S Hammond
  • L S Coghill
  • H Wen
  • R Rusinova
  • A G Clark
  • I B Levitan
  • M J Shipston
چکیده

Alternative exon splicing and reversible protein phosphorylation of large conductance calcium-activated potassium (BK) channels represent fundamental control mechanisms for the regulation of cellular excitability. BK channels are encoded by a single gene that undergoes extensive, hormonally regulated exon splicing. In native tissues BK channels display considerable diversity and plasticity in their regulation by cAMP-dependent protein kinase (PKA). Differential regulation of alternatively spliced BK channels by PKA may provide a molecular basis for the diversity and plasticity of BK channel sensitivities to PKA. Here we demonstrate that PKA activates BK channels lacking splice inserts (ZERO) but inhibits channels expressing a 59-amino acid exon at splice site 2 (STREX-1). Channel activation is dependent upon a conserved C-terminal PKA consensus motif (S869), whereas inhibition is mediated via a STREX-1 exon-specific PKA consensus site. Thus, alternative splicing acts as a molecular switch to determine the sensitivity of potassium channels to protein phosphorylation.

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عنوان ژورنال:
  • The Journal of biological chemistry

دوره 276 11  شماره 

صفحات  -

تاریخ انتشار 2001