Conclusions
Our data provide a novel mechanism whereby IKK2 regulates MLC phosphorylation as an MLCK and, thus, vascular function and blood pressure.
Objective
Therefore, we tested whether IKK2 is an MLCK in living cells and the role of IKK2 in mediating vasoconstriction and blood pressure regulation.
Results
In the present study, we showed that recombinant IKK2-phosphorylated MLC and intact myosin in vitro, and the kinetic parameters were comparable with those of the classic MLCK. Overexpression of IKK2 increased cellular MLC phosphorylation level, and pharmacological inhibition of IKK2 markedly decreased vascular smooth muscle cell MLC phosphorylation, suggesting that IKK2 is an MLCK in living cells. IKK2 inhibitors dose- and time-dependently attenuated vasoconstriction elicited by diverse agonists, suggesting the physiological importance of IKK2 as an MLCK. Vascular smooth muscle cell-specific IKK2-deficient mice had decreased aortic contractile responses, and reduced hypertensive responses to several vasoconstrictors, compared with wild-type mice, confirming the physiological importance of IKK2 as an MLCK. Conclusions: Our data provide a novel mechanism whereby IKK2 regulates MLC phosphorylation as an MLCK and, thus, vascular function and blood pressure.