Protein kinase CKIIα interacts with the Bcr moiety of Bcr/Abl and mediates proliferation of Bcr/Abl-expressing cells

The Bcr protein was originally identified because of its fusion to Abl as a consequence of the Philadelphia chromosome translocation found in chronic myelogenous and acute lymphoblastic leukemias. The Bcr moiety is essential for the transforming activity of the Bcr/Abl oncogene. In search of physiologically relevant Bcr and Bcr/Abl-interacting proteins, we performed an interaction screen in yeast using the entire Bcr protein as bait. We here report that the α catalytic subunit of protein kinase CKII strongly and specifically forms a complex with Bcr in yeast in mouse lysates. The region in Bcr responsible for CKII α binding was localized to residues 242–413. CKII α was previously shown to be involved in leukemogenesis and tumorigenesis using different experimental approaches including mouse models. Inhibition of Bcr/Abl P190 in lymphoma cells from Bcr/Abl transgenic mice using imatinib reduced CKII α activity. A highly selective inhibitor of CKII α , 4,5,6,7-tetrabromo-2-benzotriazole, inhibited the growth of murine lymphoid cells with induced P210 Bcr/Abl expression and of P190 lymphoma cells. Our results demonstrate that CKII α plays an important role in the proliferation of Bcr/Abl expressing cells, and suggests that inhibitors of CKII α may have therapeutic potential in the treatment of Bcr/Abl-positive leukemia patients.