Although the targets of CK2 are predominantly nucleus-based the protein itself is localized to both the nucleus and cytoplasm. Casein kinase 2 activity has been reported to be activated following Wnt signaling pathway activation. A Pertussis toxin-sensitive G protein and Dishevelled appear to be an intermediary between Wnt-mediated activation of the Frizzled receptor and activation of CK2. Further studies need to be done on the regulation of this protein due to the complexity of CK2 function and localization.
Phosphorylation of CK2α T344 has been shown to inhibit its proteasomal degradation and support binding to Pin1. O-GlcNAcylation at S347 antagonizes this phosphorylation and accelerates CK2α degradation. O-GlcNAcylation of CK2α has also been shown to alter the phosphoproteome, notably including many chromatin regulators such as HDAC1, HDAC2, and HCFC1.