TY - JOUR
T1 - CaMKII in the cardiovascular system
T2 - Sensing redox states
AU - Erickson, Jeffrey R.
AU - Julie He, B.
AU - Grumbach, Isabella M.
AU - Anderson, Mark E.
PY - 2011/7
Y1 - 2011/7
N2 - The multifunctional Ca2+-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 (Ca2+/ CaM). Under conditions of sustained exposure to elevated Ca2+/CaM, CaMKII transitions into a Ca2+/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 Ca2+/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 Ca2+/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.
AB - The multifunctional Ca2+-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 (Ca2+/ CaM). Under conditions of sustained exposure to elevated Ca2+/CaM, CaMKII transitions into a Ca2+/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 Ca2+/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 Ca2+/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.
UR - http://www.scopus.com/inward/record.url?scp=79960108482&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79960108482&partnerID=8YFLogxK
U2 - 10.1152/physrev.00018.2010
DO - 10.1152/physrev.00018.2010
M3 - Review article
C2 - 21742790
AN - SCOPUS:79960108482
SN - 0031-9333
VL - 91
SP - 889
EP - 915
JO - Physiological reviews
JF - Physiological reviews
IS - 3
ER -