Ca2+/calmodulin-dependent protein kinase IV stimulates nuclear factor-kappa B transactivation via phosphorylation of the p65 subunit.
Calmodulin-dependent protein kinase IV (CaMKIV) is a key mediator of Ca(2+)-induced gene expression. In this study, CaMKIV was found to directly associate with and phosphorylate the nuclear factor-kappaB (NFkappaB) component p65 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 mediator for retinoid and thyroid hormone receptors, as demonstrated by the glutathione S-transferase pull down and mammalian two hybrid assays. In addition, cotransfection of CaMKIV resulted in cytosolic translocation of the silencing mediator for retinoid and thyroid hormone receptors. Consistent with these results, cotransfected CaMKIV dramatically stimulated the NFkappaB transactivation in mammalian cells. From these results, NFkappaB is suggested to be a novel downstream effector molecule of CaMKIV.
Center for Ligand and Transcription, Chonnam National University, Kwangju 500-757, Seoul 151-742, Korea.
M K
MK
Jang
Y H
YH
Goo
Y C
YC
Sohn
Y S
YS
Kim
S K
SK
Lee
H
H
Kang
J
J
Cheong
J W
JW
Lee
D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism; D006801:Humans; D016328:NF-kappa B / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D056985:Nuclear Receptor Co-Repressor 2; D010766:Phosphorylation; D011485:Protein Binding; D021381:Protein Transport; D012097:Repressor Proteins / Q000378:metabolism; D015533:Transcriptional Activation
D004268:DNA-Binding Proteins; C539130:NCOR2 protein, human; D016328:NF-kappa B; D056985:Nuclear Receptor Co-Repressor 2; D012097:Repressor Proteins; D017871:Calcium-Calmodulin-Dependent Protein Kinases