[Has protein kinase CK2 a role in the intracellular mitogenic signalling?].
The protein kinase CK2 is an ubiquitous serine-threonine kinase found in all eukaryotic cells. Although well characterized on a biochemical ground, its role and regulation in the intact cell are not clearly understood. Its possible implication in the control of cell proliferation has been examined by several different approaches. (i) Immunocytochemical detection of CK2 revealed that whereas the signal was evenly distributed throughout cycle arrested cells in primary culture, it accumulates rapidly (30-90 min) in the nuclear compartment in cells stimulated to grow. (ii) CK2 biosynthesis is activated as an early response to growth factors in quiescent cells. The neo-synthesized kinase accumulates as the cells progress through the G1 phase. This growth factor-activated biosynthesis concerns in parallel the two kinase subunits. (iii) The kinase is activated in vitro by polyamines, which are increased in cells challenged by growth factors. Spermine binds to a specific domain of the beta subunit of CK2. (iv) In addition to phosphorylation CK2 forms a molecular complex with p53, a major negative regulator of the cell cycle. The complex was demonstrated in intact cells and reconstituted in vitro (Kd 70 nM) with purified components and shown to require the beta subunit and to result in the inhibition of p53 DNA-annealing activity. These observations suggest that CK2 and p53 may play a coordinated role in the cell response to mitogenic stimuli.
Filhol
O
O
CEA, Biochimie des Régulations Cellulaires Endocrines, INSERM Unité 244, Grenoble, France.
Leroy
D
D
Valéro
E
E
Loue-Mackenbach
P
P
Hériché
J K
JK
Goldberg
Y
Y
Cochet
C
C
Chambaz
E M
EM
D000818:Animals; D047390:Casein Kinase II; D002453:Cell Cycle; D002455:Cell Division; D006224:Cricetinae; D004347:Drug Interactions; D006133:Growth Substances / Q000378:metabolism*; D007668:Kidney / Q000166:cytology; D011073:Polyamines / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis / Q000378:metabolism*; D013347:Subcellular Fractions / Q000201:enzymology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D006133:Growth Substances; D011073:Polyamines; D016159:Tumor Suppressor Protein p53; D047390:Casein Kinase II; D017346:Protein Serine-Threonine Kinases
La protéine kinase CK2 a-t-elle une place dans la messagerie intracellulaire mitogène?