Distinct Transforming Activity of ABL Family Tyrosine Kinase Oncogenes Is Induced by Their C-Terminal Domain* - Open Journal of Blood Diseases

OJBD > Vol.3 No.3, October 2013

Distinct Transforming Activity of ABL Family Tyrosine Kinase Oncogenes Is Induced by Their C-Terminal Domain* ()

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DOI: 10.4236/ojbd.2013.33A005 3,757 Downloads 5,641 Views Citations

Author(s)

Keiko Okuda, Hideyo Hirai

Affiliation(s)

Department of Molecular Diagnostics and Therapeutics, Kyoto Prefectural University of Medicine Graduates School of Medical Science, Kyoto, Japan.
Department of Transfusion Medicine and Cell Therapy, Kyoto University Hospital, Kyoto, Japan..

ABSTRACT

The TEL/ARG oncogene is similar in structure to the TEL/ABL fusion found in human leukemia, however, we have demonstrated previously that the expression of TEL/ARG in Ba/F3 cells does not sustain strong activity of proliferation, whereas, that of TEL/ABL appeared to induce immediate cell proliferation. To study the molecular basis of the difference in the transforming activity of TEL/ARG and TEL/ABL, TEL/ARG mutants that swapped the kinase domain or C-terminus of ARG with the corresponding domain in ABL were generated, and each mutant was expressed in Ba/F3 cells. A TEL/ARG mutant containing the ABL kinase domain was similar to TEL/ARG in this study, but replacing the ARG C-terminal domain with that of ABL resulted in accelerated proliferation that was similar to that of TEL/ABL. When expressed in primary mouse bone marrow cells by retroviral transduction, spontaneous colony formation in methylcellulose culture was observed, in a fashion dependent on the C-terminal portion of ABL. These results indicate that distinct bio-phenotypes associated with these oncogenes are likely to be regulated by their C-termini, and the C-terminus of ARG contains a functional subdomain that impairs the growth signal induced by ABL family tyrosine kinase.

KEYWORDS

Leukemia; Chimeric Oncogene; ABL Family Tyrosine Kinase; Signal Transduction

Share and Cite:

K. Okuda and H. Hirai, "Distinct Transforming Activity of ABL Family Tyrosine Kinase Oncogenes Is Induced by Their C-Terminal Domain*," Open Journal of Blood Diseases, Vol. 3 No. 3A, 2013, pp. 23-33. doi: 10.4236/ojbd.2013.33A005.

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