Linked Life Data

10318802

Source:http://linkedlifedata.com/resource/pubmed/id/10318802

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
20
pubmed:dateCreated
1999-6-17
pubmed:abstractText
The human Kv1.5 potassium channel forms the IKur current in atrial myocytes and is functionally altered by coexpression with Kvbeta subunits. To explore the role of protein kinase A (PKA) phosphorylation in beta-subunit function, we examined the effect of PKA stimulation on Kv1.5 current following coexpression with either Kvbeta1.2 or Kvbeta1.3, both of which coassemble with Kv1.5 and induce fast inactivation. In Xenopus oocytes expressing Kv1.5 and Kvbeta1.3, activation of PKA reduced macroscopic inactivation with an increase in K+ current. Similar results were obtained using HEK 293 cells which lack endogenous K+ channel subunits. These effects did not occur when Kv1.5 was coexpressed with either Kvbeta1.2 or Kvbeta1.3 lacking the amino terminus, suggesting involvement of this region of Kvbeta1.3. Removal of a consensus PKA phosphorylation site on the Kvbeta1.3 NH2 terminus (serine 24), but not alternative sites in either Kvbeta1.3 or Kv1.5, resulted in loss of the functional effects of kinase activation. The effects of phosphorylation appeared to be electrostatic, as replacement of serine 24 with a negatively charged amino acid reduced beta-mediated inactivation, while substitution with a positively charged residue enhanced it. These results indicate that Kvbeta1.3-induced inactivation is reduced by PKA activation, and that phosphorylation of serine 24 in the subunit NH2 terminus is responsible.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
14
pubmed:volume
274
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
13928-32
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:10318802-Amino Acid Substitution, pubmed-meshheading:10318802-Animals, pubmed-meshheading:10318802-Cell Line, pubmed-meshheading:10318802-Consensus Sequence, pubmed-meshheading:10318802-Cyclic AMP-Dependent Protein Kinases, pubmed-meshheading:10318802-Enzyme Activation, pubmed-meshheading:10318802-Humans, pubmed-meshheading:10318802-Kv1.3 Potassium Channel, pubmed-meshheading:10318802-Kv1.5 Potassium Channel, pubmed-meshheading:10318802-Mutagenesis, Site-Directed, pubmed-meshheading:10318802-Oocytes, pubmed-meshheading:10318802-Phosphorylation, pubmed-meshheading:10318802-Potassium Channels, pubmed-meshheading:10318802-Potassium Channels, Voltage-Gated, pubmed-meshheading:10318802-Serine, pubmed-meshheading:10318802-Structure-Activity Relationship, pubmed-meshheading:10318802-Xenopus laevis
pubmed:year
1999
pubmed:articleTitle
Protein kinase A phosphorylation alters Kvbeta1.3 subunit-mediated inactivation of the Kv1.5 potassium channel.
pubmed:affiliation
Department of Physiology and Biochemistry and Molecular Biology, Colorado State University, Ft. Collins, Colorado 80523, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't