Protein kinase CK2alpha is a target for the Abl and Bcr-Abl tyrosine kinases.
Protein kinase CK2 is a ubiquitous serine-threonine kinase in which a catalytic alpha subunit often associates with a beta subunit. CK2alpha is required for cell survival in yeast and has been proposed to be involved in cell growth control; however, its regulation in cells remains unclear. Here we present evidence that CK2alpha may be an associated substrate for the normal and oncogenic forms of the Abl tyrosine kinase. By probing CK2alpha with anti-phosphotyrosine antibodies, we found that CK2alpha can be phosphorylated on tyrosine in quiescent cells. In vitro phosphorylation of CK2alpha-containing immunoprecipitates showed that CK2alpha is substrate of an associated tyrosine kinase activity. Immunoprecipitation experiments revealed that CK2alpha is associated with normal c-Abl in mouse NIH3T3 fibroblasts and with the Bcr-Abl fusion protein in K562 human myeloid leukemia cells. Coexpression of Bcr-Abl and CK2alpha in NIH3T3 cells also leads to the formation of a Bcr-Abl/CK2alpha complex and to the inhibition of CK2alpha activity. Bcr-Abl-induced inhibition of CK2alpha could be reverted by incubating CK2alpha with a tyrosine phosphatase. These observations clearly support the idea that a signal transduction pathway contributes to CK2 regulation and point to CK2alpha as a possible mediator of Bcr-Abl effects.
Hériché
J K
JK
INSERM U244 and CEA/Grenoble, Département de Biologie Moléculaire et Structurale, Laboratoire de Biochimie des Régulations Cellulaires Endocrines, France.
Chambaz
E M
EM
D016475:3T3 Cells; D000818:Animals; D047390:Casein Kinase II; D002645:Chickens; D016044:Fusion Proteins, bcr-abl / Q000378:metabolism*; D006801:Humans; D051379:Mice; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D016315:Proto-Oncogene Proteins c-abl / Q000378:metabolism*; D013379:Substrate Specificity; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism
D014443:Tyrosine; D016044:Fusion Proteins, bcr-abl; D016315:Proto-Oncogene Proteins c-abl; D047390:Casein Kinase II; D017346:Protein Serine-Threonine Kinases