Casein kinase Iε associates with and phosphorylates the tight junction protein occludin

Occludin is an integral-membrane protein that contributes to tight junction function. We have identified casein kinase Iε (CKIε) as a binding partner for the C-terminal cytoplasmic domain of occludin by yeast two-hybrid screening. CKIε phosphorylated occludin and co-localised and co-immunoprecipitated with occludin from human endothelial cells. Amino acids 265–318 of occludin were sufficient for CKIε binding and phosphorylation. Deletion of the C-terminal 48 amino acids of occludin increased CKIε binding and phosphorylation, suggesting that this region inhibits CKIε binding. These data identify CKIε as a novel occludin kinase that may be important for the regulation of occludin.