Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
32
pubmed:dateCreated
2004-8-12
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.
pubmed:grant
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, http://linkedlifedata.com/resource/pubmed/commentcorrection/15280542-11309619, http://linkedlifedata.com/resource/pubmed/commentcorrection/15280542-11331373, http://linkedlifedata.com/resource/pubmed/commentcorrection/15280542-11514553, http://linkedlifedata.com/resource/pubmed/commentcorrection/15280542-11583807, http://linkedlifedata.com/resource/pubmed/commentcorrection/15280542-11604135, http://linkedlifedata.com/resource/pubmed/commentcorrection/15280542-11738032, http://linkedlifedata.com/resource/pubmed/commentcorrection/15280542-12019304, http://linkedlifedata.com/resource/pubmed/commentcorrection/15280542-12161564, http://linkedlifedata.com/resource/pubmed/commentcorrection/15280542-12509433, http://linkedlifedata.com/resource/pubmed/commentcorrection/15280542-14561822, http://linkedlifedata.com/resource/pubmed/commentcorrection/15280542-14985765, http://linkedlifedata.com/resource/pubmed/commentcorrection/15280542-1646298, http://linkedlifedata.com/resource/pubmed/commentcorrection/15280542-1710783, http://linkedlifedata.com/resource/pubmed/commentcorrection/15280542-2553198, http://linkedlifedata.com/resource/pubmed/commentcorrection/15280542-7517033, http://linkedlifedata.com/resource/pubmed/commentcorrection/15280542-7687074, http://linkedlifedata.com/resource/pubmed/commentcorrection/15280542-7790924, http://linkedlifedata.com/resource/pubmed/commentcorrection/15280542-7993625, http://linkedlifedata.com/resource/pubmed/commentcorrection/15280542-8568673, http://linkedlifedata.com/resource/pubmed/commentcorrection/15280542-8621576, http://linkedlifedata.com/resource/pubmed/commentcorrection/15280542-9390519, http://linkedlifedata.com/resource/pubmed/commentcorrection/15280542-9390520, http://linkedlifedata.com/resource/pubmed/commentcorrection/15280542-9391153, http://linkedlifedata.com/resource/pubmed/commentcorrection/15280542-9545224, http://linkedlifedata.com/resource/pubmed/commentcorrection/15280542-9614096, http://linkedlifedata.com/resource/pubmed/commentcorrection/15280542-9687354
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0027-8424
pubmed:author
pubmed:issnType
Print
pubmed:day
10
pubmed:volume
101
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
11897-902
pubmed:dateRevised
2009-11-18
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Distinct stoichiometry of BKCa channel tetramer phosphorylation specifies channel activation and inhibition by cAMP-dependent protein kinase.
pubmed:affiliation
Membrane Biology Group, Division of Biomedical Science, University of Edinburgh, Edinburgh EH8 9XD, United Kingdom.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't