Inhibitor κB Kinase 2 Is a Myosin Light Chain Kinase in Vascular Smooth Muscle

Rationale:Myosin light chain (MLC) phosphorylation determines vascular contractile status. In addition to the classic Ca2+-dependent MLC kinase (MLCK), another unidentified kinase(s) also contributes to MLC phosphorylation in living cells. Inhibitor κB kinase 2 (IKK2)–deficient mouse embryonic fibroblasts demonstrate abnormal morphology and migration, suggesting that IKK2 may be involved in MLC phosphorylation. Objective:Therefore, we tested whether IKK2 is an MLCK in living cells and the role of IKK2 in mediating vasoconstriction and blood pressure regulation. Methods and 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-...