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Chronic elevation of calmodulin in the ventricles of transgenic mice increases the autonomous activity of calmodulin-dependent protein kinase II, which regulates atrial natriuretic factor gene expression.

Publication ,  Journal Article
Colomer, JM; Means, AR
Published in: Mol Endocrinol
August 2000

Although isoforms of Ca2+/calmodulin-dependent protein kinase II (CaMKII) have been implicated in the regulation of gene expression in cultured cells, this issue has yet to be addressed in vivo. We report that the overexpression of calmodulin in ventricular myocytes of transgenic mice results in an increase in the Ca2+/calmodulin-independent activity of endogenous CaMKII. The calmodulin transgene is regulated by a 500-bp fragment of the atrial natriuretic factor (ANF) gene promoter which, based on cell transfection studies, is itself known to be regulated by CaMKII. The increased autonomous activity of CaMKII maintains the activity of the transgene and establishes a positive feed-forward loop, which also extends the temporal expression of the endogenous ANF promoter in ventricular myocytes. Both the increased activity of CaMKII and transcriptional activation of ANF are highly selective responses to the chronic overexpression of calmodulin. These results indicate that CaMKII can regulate gene expression in vivo and suggest that this enzyme may represent the Ca2+-dependent target responsible for reactivation of the ANF gene during ventricular hypertrophy.

Duke Scholars

Published In

Mol Endocrinol

DOI

ISSN

0888-8809

Publication Date

August 2000

Volume

14

Issue

8

Start / End Page

1125 / 1136

Location

United States

Related Subject Headings

  • Ventricular Function
  • Promoter Regions, Genetic
  • Mice, Transgenic
  • Mice
  • Gene Expression Regulation
  • Endocrinology & Metabolism
  • Cardiomegaly
  • Calmodulin
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
 

Citation

APA
Chicago
ICMJE
MLA
NLM

Published In

Mol Endocrinol

DOI

ISSN

0888-8809

Publication Date

August 2000

Volume

14

Issue

8

Start / End Page

1125 / 1136

Location

United States

Related Subject Headings

  • Ventricular Function
  • Promoter Regions, Genetic
  • Mice, Transgenic
  • Mice
  • Gene Expression Regulation
  • Endocrinology & Metabolism
  • Cardiomegaly
  • Calmodulin
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2