Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
49
pubmed:dateCreated
1998-1-8
pubmed:abstractText
Cultured neonatal ventricular myocytes display features of myocardial hypertrophy including increased cell size, myofilament organization, and reexpression of the embryonic gene for atrial natriuretic factor (ANF). KN-93, an inhibitor of multifunctional Ca2+/calmodulin-dependent protein kinase (CaM kinase II), blocked the induction of these responses by the alpha1-adrenergic receptor agonist phenylephrine, whereas its inactive analog KN-92 did not. To directly determine whether CaM kinase II could regulate ANF gene expression, we transiently expressed each of three isoforms of CaM kinase II (alpha, deltaB, and deltaC) along with an ANF promoter/luciferase reporter gene. The deltaB isoform markedly increased luciferase gene expression, whereas comparable levels of the deltaC and alpha isoforms were ineffective. Expression of deltaB-CaM kinase II also potentiated phenylephrine-mediated ANF gene expression, and this effect was blocked by KN-93 but not by KN-92. The ability of deltaB-CaM kinase II to transactivate a truncated ANF promoter, containing a serum response element (SRE) required for phenylephrine-inducible gene expression, was lost when this SRE was mutated. The deltaB isoform of CaM kinase II has been shown to exhibit nuclear localization. Coexpression of the non-nuclear deltaC or alpha isoforms, which can form multimers with the deltaB isoform, prevented the nuclear localization of deltaB-CaM kinase II and also blocked its effects on ANF reporter gene and protein expression. In addition, a chimeric alpha-CaM kinase II which contains the nuclear localization signal of the deltaB isoform was able to induce ANF reporter gene expression, albeit to a lesser extent than deltaB-CaM kinase II. These data are the first to assign a function to the deltaB isoform of CaM kinase II and to link its nuclear localization to subsequent activation of cardiac gene expression.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
5
pubmed:volume
272
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
31203-8
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
1997
pubmed:articleTitle
The nuclear deltaB isoform of Ca2+/calmodulin-dependent protein kinase II regulates atrial natriuretic factor gene expression in ventricular myocytes.
pubmed:affiliation
Department of Pharmacology and Biomedical Sciences Graduate Program, University of California at San Diego, La Jolla, California 92093, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't