Ca2+/calmodulin-dependent protein kinase IV stimulates nuclear factor-kappa B transactivation via phosphorylation of the p65 subunit

Calmodulin-dependent protein kinase TV (CaMKIV) is a key mediator of Ca2+-i nduced gene expression. In this study, CaMKIV was found to directly associa te with and phosphorylate the nuclear factor-kappaB (NF kappaB) component p 65 both in vitro and in vivo. The phosphorylation of p65 by CaMKIV resulted in recruitment of transcription coactivator cAMP-response element-binding protein-binding protein and concomitant release of corepressor silencing me diator for retinoid and thyroid hormone receptors, as demonstrated by the g lutathione S-transferase pull down and mammalian two hybrid assays. In addi tion, cotransfection of CaMKIV resulted in cytosolic translocation of the s ilencing mediator for retinoid and thyroid hormone receptors. Consistent wi th these results, cotransfected CaMKIV dramatically stimulated the NF kappa B transactivation in mammalian cells. From these results, NF kappaB is sugg ested to be a novel downstream effector molecule of CaMKIV.