Protein casein kinase 2 (CK2), a multifunctional enzyme commonly considered a stable tetramer with two catalytic α subunits and two regulatory β subunits, has substrates in various cellular compartments. Filhol et al. used live-cell fluorescence imaging to track the subcellular localization of CK2 subunit mutants labeled with green fluorescent protein (GFP) or GFP derivatives. They found that nuclear import and export of CK2 α and β subunits were regulated independently. GFP-CK2α constructs transfected into NIH 3T3 cells were predominantly localized to the nucleus, a localization that depended in part on a functional nuclear localization signal in the CK2α NH 2 -terminal region, and microinjected His 6 -tagged GFP-CK2α rapidly translocated to the nucleus. CK2β also accumulated in the nucleus; this depended on a zinc finger motif involved in CK2β dimerization, but did not depend on CK2β association with CK2α. The authors fused stably transfected NIH 3T3 cells with untransfected HeLa cells to demonstrate shuttling of CK2α, but not CK2β, between the nucleus and the cytoplasm. Dual-color image analysis of differently labeled cotransfected α and β subunits, however, showed a predominantly cytoplasmic location for both subunits, and the microinjected holoenzyme, unlike the individual subunits, did not accumulate in the nucleus. Fibroblast growth factor 2, which binds to and activates the holoenzyme, triggered nuclear accumulation. Association of CK2β with CK2α, which is known to affect CK2α substrate specificity, may thus also regulate the subcellular distribution of CK2α and thereby its accessibility to various substrates. O. Filhol, A. Nueda, V. Martel, D. Gerber-Scokaert, M. J. Benitez, C. Souchier, Y. Saoudi, C. Cochet, Live-cell fluorescence imaging reveals the dynamics of protein kinase CK2 individual subunits. Mol. Cell. Biol . 23 , 975-987 (2003). [Abstract] [Full Text]