The 'regulatory' beta-subunit of protein kinase CK2 negatively influences p53-mediated allosteric effects on Chk2 activation.
The 'regulatory' beta-subunit of protein kinase CK2 has previously been shown to interact with protein kinases such as A-Raf, c-Mos, Lyn and Chk1 in addition to the catalytic subunit of CK2. Sequence alignments suggest that these interactions have a structural basis, and hence other protein kinases harboring corresponding sequences may be potential interaction partners for CK2beta. We show here that Chk2 specifically interacts with CK2beta in vitro and in cultured cells, and that activation of Chk2 leads to a reduction of this interaction. Additionally, we show that the presence of the CK2beta-subunit significantly reduces the Chk2-catalysed phosphorylation of p53 in vitro. These findings support the notion that CK2beta can act as a general modulator of remote docking sites in protein kinase--substrate interactions.
Bjørling-Poulsen
Marina
M
Institut for Biokemi og Molekylaer Biologi, Syddansk Universitet, Odense, Denmark.
Siehler
Simone
S
Wiesmüller
Lisa
L
Meek
David
D
Niefind
Karsten
K
Issinger
Olaf-Georg
OG
D000494:Allosteric Regulation; D000818:Animals; D019556:COS Cells; D047390:Casein Kinase II / Q000378:metabolism* / Q000502:physiology*; D020134:Catalytic Domain; D064447:Checkpoint Kinase 2; D002522:Chlorocebus aethiops; D004789:Enzyme Activation; D016158:Genes, p53; D006801:Humans; D010766:Phosphorylation; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D016159:Tumor Suppressor Protein p53; D064447:Checkpoint Kinase 2; C578634:CHEK2 protein, human; D047390:Casein Kinase II; D017346:Protein Serine-Threonine Kinases