Protein Kinase CK2: A Global Coordinator of Cell Behavior
Amil da Costa Jacob Ramalho, J.M. de
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Cellular adaptation to the constant changes in internal and environmental conditions is a key strategy for cell survival and development. In eukaryotes, cellular adaptation generally depends on the regulated activation of well-defined and condition-specific molecular signaling cascades that activate terminal effectors responsible for altering the cell behavior. In contrast, the activity of the atypically regulated protein kinase CK2 has been puzzling researchers for decades and a concrete model of its function in cells remains to be established. The highly pleiotropic CK2 is conserved and ubiquitously expressed in all eukaryotic cells, localizes to virtually all subcellular structures, and is constitutively active irrespective of the cellular conditions. Nevertheless, distinct cellular conditions are known to differentially modulate the catalytic activity, subcellular localization, and substrate preference of CK2, eliciting specific CK2-driven cellular responses. Classically, CK2 has been associated with growth promotion since it acts at multiple levels to induce growth signaling pathways and suppress apoptosis. Mounting evidence suggests that CK2 directly regulates an even wider range of signal transduction pathways in development and stress response, as well as most of the conserved eukaryotic mechanisms required for gene expression, growth, and cellular integrity. In this review, I will focus on discussing relevant information concerning the regulation of CK2 and its activities in signal transduction and regulation of vital cellular mechanisms. I will further discuss how CK2 can act as a crucial factor in determining cellular behavior and adaptation by integrating numerous stimuli, coordinating diverse signaling pathways, and directly modulating the activity of cellular mechanisms.