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

Oncogene volume 22, pages 8255–8262 (2003)Cite this article

A Corrigendum to this article was published on 19 August 2004

Abstract

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 CKIIα binding was localized to residues 242–413. CKIIα 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 CKIIα activity. A highly selective inhibitor of CKIIα, 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 CKIIα plays an important role in the proliferation of Bcr/Abl expressing cells, and suggests that inhibitors of CKIIα may have therapeutic potential in the treatment of Bcr/Abl-positive leukemia patients.

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Acknowledgements

We thank Dr Flavio Meggio (Universita di Padova, Dipartimento di Chimica Biologica, Italy) for the generous gift of TBB, Dr Ron de Jong for initial work with the BCR exon 1 construct and deletion mutants and Dr Emmanuelle Faure for the initial work on the yeast two-hybrid screen. We thank Dr Clemens Schmitt for suggestions on homogenizing lymphoma cells. Abl (clone 3F12) monoclonal antibodies were a kind gift of Dr Ravi Salgia (Dana-Farber Cancer Institute, Boston, MA, USA). We thank Dr George Daley for the generous gift of the TonB.210 cell line. This work was supported by Public Health Service Grants CA 50248 and CA 90321 (NH), grants from the TJ Martell Foundation (to NH and JG) and a grant from the Kenneth T and Eileen L Norris Foundation (to JG).

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  1. Anja Reichert

    Present address: MTM Laboratories AG, Im Neuerheimer Feld 583, D-69120, Heidelberg, Germany

Authors and Affiliations

  1. Division of Hematology/Oncology, Section of Molecular Carcinogenesis, Ms#54, Childrens Hospital of Los Angeles Research Institute 4650 Sunset Boulevard, Los Angeles, 90027, CA, USA

    Suparna Mishra, Anja Reichert, Jess Cunnick, Dinithi Senadheera, Bianca Hemmeryckx, Nora Heisterkamp & John Groffen

  2. Keck School of Medicine of the University of Southern California, 4650 Sunset Boulevard, Los Angeles, 90027, CA, USA

    Suparna Mishra, Anja Reichert, Jess Cunnick, Dinithi Senadheera, Bianca Hemmeryckx, Nora Heisterkamp & John Groffen

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Correspondence to John Groffen.

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Mishra, S., Reichert, A., Cunnick, J. et al. Protein kinase CKIIα interacts with the Bcr moiety of Bcr/Abl and mediates proliferation of Bcr/Abl-expressing cells. Oncogene 22, 8255–8262 (2003). https://doi.org/10.1038/sj.onc.1207156

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