Skip to main page content
U.S. flag

An official website of the United States government

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2015 Aug 25:6:178.
doi: 10.3389/fphar.2015.00178. eCollection 2015.

Regulation of CaMKII signaling in cardiovascular disease

Affiliations
Review

Regulation of CaMKII signaling in cardiovascular disease

Mariya Y Mollova et al. Front Pharmacol. .

Abstract

Heart failure (HF) is a major cause of death in the developed countries (Murray and Lopez, 1996; Koitabashi and Kass, 2012). Adverse cardiac remodeling that precedes heart muscle dysfunction is characterized by a myriad of molecular changes affecting the cardiomyocyte. Among these, alterations in protein kinase pathways play often an important mediator role since they link upstream pathologic stress signaling with downstream regulatory programs and thus affect both the structural and functional integrity of the heart muscle. In the context of cardiac disease, a profound understanding for the overriding mechanisms that regulate protein kinase activity (protein-protein interactions, post-translational modifications, or targeting via anchoring proteins) is crucial for the development of specific and effective pharmacological treatment strategies targeting the failing myocardium. In this review, we focus on several mechanisms of upstream regulation of Ca(2+)-calmodulin-dependent protein kinase II that play a relevant pathophysiological role in the development and progression of cardiovascular disease; precise targeting of these mechanisms might therefore represent novel and promising tools for prevention and treatment of HF.

Keywords: CaMKII; enzymatic activity; heart failure; post-translational modifications; sub-cellular localization.

PubMed Disclaimer

Figures

FIGURE 1
FIGURE 1
(A) A schematic representation of a CaMKII monomer, consisting of a (1) N-terminal catalytic domain, (2) regulatory domain, and (3) a C-terminal association domain. The most rigorously studied sites for different post-translational modifications (PTMs) are highlighted in red below. (B) The association domain (green), which is responsible for assembly into the holoenzyme, contains a hypervariable domain. Twelve to fourteen of these subunits multimerize together to form the CaMKII holoenzyme.

Similar articles

Cited by

References

    1. Anderson M. E., Brown J. H., Bers D. M. (2011). CaMKII in myocardial hypertrophy and heart failure. J. Mol. Cell. Cardiol. 51, 468–473. 10.1016/j.yjmcc.2011.01.012 - DOI - PMC - PubMed
    1. Aurora A. B., Mahmoud A. I., Luo X., Johnson B. A., Van Rooij E., Matsuzaki S., et al. (2012). MicroRNA-214 protects the mouse heart from ischemic injury by controlling Ca2+ overload and cell death. J. Clin. Invest. 122, 1222–1232. 10.1172/JCI59327 - DOI - PMC - PubMed
    1. Backs J., Backs T., Bezprozvannaya S., Mckinsey T. A., Olson E. N. (2008). Histone deacetylase 5 acquires calcium/calmodulin-dependent kinase II responsiveness by oligomerization with histone deacetylase 4. Mol. Cell. Biol. 28, 3437–3445. 10.1128/MCB.01611-07 - DOI - PMC - PubMed
    1. Backs J., Song K., Bezprozvannaya S., Chang S., Olson E. N. (2006). CaM kinase II selectively signals to histone deacetylase 4 during cardiomyocyte hypertrophy. J. Clin. Invest. 116, 1853–1864. 10.1172/JCI27438 - DOI - PMC - PubMed
    1. Backs J., Worst B. C., Lehmann L. H., Patrick D. M., Jebessa Z., Kreusser M. M., et al. (2011). Selective repression of MEF2 activity by PKA-dependent proteolysis of HDAC4. J. Cell Biol. 195, 403–415. 10.1083/jcb.201105063 - DOI - PMC - PubMed