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CaMKII in the cardiovascular system: sensing redox states
JR Erickson, BJ He, IM Grumbach... - Physiological ..., 2011 - Am Physiological Soc Abstract The multifunctional Ca 2+-and calmodulin-dependent protein kinase II (Ca MKII) is now recognized to play a central role in pathological events in the cardiovascular system. Ca MKII has diverse downstream targets that promote vascular disease, heart failure, and ...
The multifunctional Ca2+- and calmodulin-dependent protein kinase II (Ca MKII) is now recognized to play a central role in pathological events in the cardiovascular system. Ca MKII has diverse downstream targets that promote vascular disease, heart failure, and arrhythmias, so improved understanding of Ca MKII signaling has the potential to lead to new therapies for cardiovascular disease. Ca MKII is a multimeric serine-threonine kinase that is initially activated by binding calcified calmodulin (Ca2+/Ca M). Under conditions of sustained exposure to elevated Ca2+/Ca M, Ca MKII transitions into a Ca2+/Ca M-autonomous enzyme by two distinct but parallel processes. Autophosphorylation of threonine-287 in the Ca MKII regulatory domain “traps” Ca MKII into an open configuration even after Ca2+/Ca M unbinding. More recently, our group identified a pair of methionines (281/282) in the Ca MKII regulatory domain that undergo a partially reversible oxidation which, like autophosphorylation, prevents Ca MKII from inactivating after Ca2+/Ca M unbinding. Here we review roles of Ca MKII in cardiovascular disease with an eye to understanding how Ca MKII 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.
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CaMKII in the cardiovascular system: sensing redox states |
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