Abstract
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.
Original language | English |
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Pages (from-to) | 7717-7720 |
Number of pages | 4 |
Journal | Journal of Biological Chemistry |
Volume | 276 |
Issue number | 11 |
DOIs | |
Publication status | Published - 16 Mar 2001 |
Keywords
- Alternative Splicing
- Animals
- Cyclic AMP
- Cyclic AMP-Dependent Protein Kinases
- Exons
- Mice
- Phosphorylation
- Potassium Channels
- Proteins
- Structure-Activity Relationship