rdf:type |
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lifeskim:mentions |
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pubmed:issue |
32
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pubmed:dateCreated |
2004-8-12
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pubmed:abstractText |
Large conductance voltage- and calcium-activated potassium (BK(Ca)) channels are important signaling molecules that are regulated by multiple protein kinases and protein phosphatases at multiple sites. The pore-forming alpha-subunits, derived from a single gene that undergoes extensive alternative pre-mRNA splicing, assemble as tetramers. Although consensus phosphorylation sites have been identified within the C-terminal domain of alpha-subunits, it is not known whether phosphorylation of all or single alpha-subunits within the tetramer is required for functional regulation of the channel. Here, we have exploited a strategy to study single-ion channels in which both the alpha-subunit splice-variant composition is defined and the number of consensus phosphorylation sites available within each tetramer is known. We have used this approach to demonstrate that cAMP-dependent protein kinase (PKA) phosphorylation of the conserved C-terminal PKA consensus site (S899) in all four alpha-subunits is required for channel activation. In contrast, inhibition of BK(Ca) channel activity requires phosphorylation of only a single alpha-subunit at a splice insert (STREX)-specific PKA consensus site (S4(STREX)). Thus, distinct modes of BK(Ca) channel regulation by PKA phosphorylation exist: an "all-or-nothing" rule for activation and a "single-subunit" rule for inhibition. This essentially digital regulation has important implications for the combinatorial and conditional regulation of BK(Ca) channels by reversible protein phosphorylation.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/15280542-10218112,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15280542-10660522,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15280542-11057658,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/15280542-9687354
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pubmed:language |
eng
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pubmed:journal |
|
pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0027-8424
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
10
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pubmed:volume |
101
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
11897-902
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:15280542-Animals,
pubmed-meshheading:15280542-Binding Sites,
pubmed-meshheading:15280542-Calcium,
pubmed-meshheading:15280542-Consensus Sequence,
pubmed-meshheading:15280542-Cyclic AMP-Dependent Protein Kinases,
pubmed-meshheading:15280542-Electrophysiology,
pubmed-meshheading:15280542-Mice,
pubmed-meshheading:15280542-Phosphorylation,
pubmed-meshheading:15280542-Potassium Channels,
pubmed-meshheading:15280542-Protein Isoforms,
pubmed-meshheading:15280542-Protein Structure, Quaternary,
pubmed-meshheading:15280542-Protein Subunits
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pubmed:year |
2004
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pubmed:articleTitle |
Distinct stoichiometry of BKCa channel tetramer phosphorylation specifies channel activation and inhibition by cAMP-dependent protein kinase.
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pubmed:affiliation |
Membrane Biology Group, Division of Biomedical Science, University of Edinburgh, Edinburgh EH8 9XD, United Kingdom.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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