PROTEIN-KINASE CK2-ALPHA IS A TARGET FOR THE ABL AND BCR-ABL TYROSINEKINASES

Protein kinase CK2 is a ubiquitous serine-threonine kinase in which a catalytic alpha subunit often associates with a beta subunit, CK2 alph a is required for cell survival in yeast and has been proposed to be i nvolved in cell growth control; however, its regulation in cells remai ns unclear. Here we present evidence that CK2 alpha may be an associat ed substrate for the normal and oncogenic forms of the Abl tyrosine ki nase. By probing CK2 alpha with antiphosphotyrosine antibodies, we fou nd that CK2 alpha can be phosphorylated on tyrosine in quiescent cells . In vitro phosphorylation of CK2 alpha-containing immunoprecipitates showed that CK2 alpha is substrate of an associated tyrosine kinase ac tivity. Immunoprecipitation experiments revealed that CK2 alpha is ass ociated 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 CK2 alpha in NIH3T3 cells also leads to the formation of a Bcr-Abl/CK2 alpha complex and to the inhibition of CK2 alpha acti vity, Bcr-Abl-induced inhibition of CK2 alpha could be reverted by inc ubating CK2 alpha with a tyrosine phosphatase. These observations clea rly support the idea that a signal transduction pathway contributes to CK2 regulation and point to CK2 alpha as a possible mediator of Bcr-A bl effects.