The raison D'Etre of constitutively active protein kinases: The lesson of CK2

Protein kinases generally are tightly controlled signaling molecules that are switched on only in response to specific stimuli. Exceptionally few protein kinases are constitutively active, the most striking example being provided by CK2 (formerly casein kinase 2). Owing to unique structural features, the catalytic activity of CK2 is constantly on, although its targeting can be deeply influenced by the association of its two catalytic subunits (alpha and/or alpha') with a dimeric non catalytic beta subunit. Constitutive activity of CK2 reflects its extraordinary pleiotropy documented by its growing list of >300 protein substrates and is consistent with emerging evidence that CK2 plays an essential role in the cell by counteracting premature and/or unscheduled apoptosis, thus ensuring cell survival under stress conditions.