Journal article
CaMKII in the Cardiovascular System: Sensing Redox States
Physiological reviews, Vol.91(3), pp.889-915
07/2011
DOI: 10.1152/physrev.00018.2010
PMCID: PMC3732780
PMID: 21742790
Abstract
The multifunctional Ca
2+
and calmodulin-dependent protein kinase II (CaMKII) is now recognized to play a central role in pathological events in the cardiovascular system. CaMKII has diverse downstream targets that promote vascular disease, heart failure and arrhythmias, so improved understanding of CaMKII signaling has the potential to lead to new therapies for cardiovascular disease. CaMKII is a multimeric serine-threonine kinase that is initially activated by binding calcified calmodulin (Ca
2+
/CaM). Under conditions of sustained exposure to elevated Ca
2+
/CaM CaMKII transitions into a Ca
2+
/CaM-autonomous enzyme by two distinct but parallel processes. Autophosphorylation of threonine 287 in the CaMKII regulatory domain ‘traps’ CaMKII into an open configuration even after Ca
2+
/CaM unbinding. More recently, our group identified a pair of methionines (281/282) in the CaMKII regulatory domain that undergo a partially reversible oxidation which, like autophosphorylation, prevents CaMKII from inactivating after Ca
2+
/CaM unbinding. Here we review roles of CaMKII in cardiovascular disease with an eye to understanding how CaMKII may act as a transduction signal to connect pro-oxidant conditions into specific downstream pathological effects that are relevant to rare and common forms of cardiovascular disease.
Details
- Title: Subtitle
- CaMKII in the Cardiovascular System: Sensing Redox States
- Creators
- Jeffrey R Erickson - Department of Pharmacology, University of California at DavisB. Julie He - Department of Molecular Physiology & Biophysics, University of Iowa, Carver College of MedicineIsabella M Grumbach - Department of Internal Medicine, Division of Cardiovascular Medicine, University of Iowa Carver College of MedicineMark E Anderson - Department of Molecular Physiology & Biophysics, University of Iowa, Carver College of Medicine
- Resource Type
- Journal article
- Publication Details
- Physiological reviews, Vol.91(3), pp.889-915
- DOI
- 10.1152/physrev.00018.2010
- PMID
- 21742790
- PMCID
- PMC3732780
- NLM abbreviation
- Physiol Rev
- ISSN
- 0031-9333
- eISSN
- 1522-1210
- Grant note
- R01 HL062494 || HL / National Heart, Lung, and Blood Institute : NHLBI R01 HL079031 || HL / National Heart, Lung, and Blood Institute : NHLBI R01 HL070250 || HL / National Heart, Lung, and Blood Institute : NHLBI
- Language
- English
- Date published
- 07/2011
- Academic Unit
- Cardiovascular Medicine; Radiation Oncology; Internal Medicine
- Record Identifier
- 9984094337402771
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