CASEIN-KINASE-2 AND THE CELL RESPONSE TO GROWTH-FACTORS

Different approaches have been followed with the aim of delineating a possible role of casein kinase 2 (CK2) in the mitogenic signalling in response to cell growth factors. (a) Immunocytochemical detection of C K2 showed that while the kinase is evenly distributed throughout cycle arrested cells, it becomes preferentially associated with the nuclear compartment in actively growing cells; (b) CK2 biosynthesis is activa ted as an early response of quiescent cells to growth factors. The new ly synthesized CK2 steadily accumulates as the cells progress through the G(1) phase. This growth factor-induced CK2 biosynthesis involves i n parallel the two alpha and beta subunits of the kinase, with no dete ctable preferential subcellular localization of the newly synthesized enzyme; and (c) In addition to substrate phosphorylation, CK2 may form molecular complexes with cell components of functional significance. Such is the case with the protein p53, a major negative regulator of t he cell cycle. CK2 forms a high affinity association (Kd 70 nM) with p 53, through its beta subunit. The complex dissociates in the presence of adenosine triphosphate (ATP). These observations suggest that CK2 a nd p53 may play a coordinated regulatory role in the cell response to growth factors.