Selectivity of 4,5,6,7‐tetrabromobenzotriazole, an ATP site‐directed inhibitor of protein kinase CK2 (‘casein kinase‐2’)

[摘要]

The specificity of 4,5,6,7-tetrabromo-2-azabenzimidazole (TBB), an ATP/GTP competitive inhibitor of protein kinase casein kinase-2 (CK2), has been examined against a panel of 33 protein kinases, either Ser/Thr- or Tyr-specific. In the presence of 10 μM TBB (and 100 μM ATP) only CK2 was drastically inhibited (>85%) whereas three kinases (phosphorylase kinase, glycogen synthase kinase 3β and cyclin-dependent kinase 2/cyclin A) underwent moderate inhibition, with IC₅₀ values one–two orders of magnitude higher than CK2 (IC₅₀=0.9 μM). TBB also inhibits endogenous CK2 in cultured Jurkat cells. A CK2 mutant in which Val66 has been replaced by alanine is much less susceptible to inhibition by TBB as well as by another ATP competitive inhibitor, emodin. These data show that TBB is a quite selective inhibitor of CK2, that can be used in cell-based assays.

[学科分类] 生物化学/生物物理

[关键词] Inhibitor;Protein kinase;Casein kinase;Casein kinase-2;Protein phosphorylation;OA;okadaic acid;TBB;4;5;6;7-tetrabromo-2-azabenzimidazole or 4;5;6;7-tetrabromobenzotriazole;DRB;1-(β-D-ribofuranosyl)-5;6-dichlorobenzimidazole;HS1;hematopoietic lineage cell-specific protein 1;MAPK;mitogen-activated protein kinase;MKK;MAPK kinase (also called MEK);ERK;extracellular signal-regulated kinase;JNK;c-Jun N-terminal kinase;SAPK;stress-activated protein kinase;MAPKAP;MAPK-activated protein kinase;MSK;mitogen- and stress-activated protein kinase;PRAK;p38-regulated/activated kinase;PKA;cAMP-dependent protein kinase;PKC;protein kinase C;PDK;3-phosphoinositide-dependent kinase;PKB;protein kinase B (also called Akt);SGK;serum- and glucocorticoid-induced kinase;p70S6K;p70 ribosomal protein S6 kinase;GSK3;glycogen synthase kinase 3;ROCK;Rho-dependent protein kinase;AMPK;AMP-activated protein kinase;CHK;checkpoint kinase;PHK;phosphorylase kinase;CDK;cyclin-dependent kinase;CK;casein kinase;nCK;native casein kinase;rCK;recombinant casein kinase;G-CK;Golgi casein kinase;CSK;C-terminal Src kinase