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Circ Res. 2013 Aug 16;113(5):562-70. doi: 10.1161/CIRCRESAHA.113.301510. Epub 2013 Jul 1.

Inhibitor κB kinase 2 is a myosin light chain kinase in vascular smooth muscle.

Author information

1
Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS, USA. yingzhekang@hotmail.com

Abstract

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-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.

KEYWORDS:

IKK2; MLC; blood pressure; blood vessels; hypertension; muscle, smooth, vascular; myosins; phosphorylation

PMID:
23817200
PMCID:
PMC3970202
DOI:
10.1161/CIRCRESAHA.113.301510
[Indexed for MEDLINE]
Free PMC Article
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