Affiliation:
1. Department of Pharmacology and Cancer Biology Duke University Medical Center Durham, North Carolina 27710
Abstract
Abstract
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 feedforward 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.
Subject
Endocrinology,Molecular Biology,General Medicine
Reference65 articles.
1. Calcium/calmodulin-dependent protein kinases.;Schulman,1999
2. Sensitivity of CaM kinase II to the frequency of Ca2+ oscillations.;De Koninck;Science,1998
3. Calmodulin trapping by calcium-calmodulin-dependent protein kinase.;Meyer;Science,1992
4. Sequences of autophosphorylation sites in neuronal type II CaM kinase that control Ca2+-independent activity.;Miller;Neuron,1988
5. Ca2+/calmodulin-dependent protein kinase II. Identification of a regulatory autophosphorylation site adjacent to the inhibitory and calmodulin-binding domains.;Schworer;J Biol Chem,1988
Cited by
26 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献