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

• 作者: Hideyo Hirai Keiko Okuda
• 来源期刊: 血液病期刊(英文)
• 学科: 医学
• 关键词: Leukemia CHIMERIC ONCOGENE ABL FAMILY TYROSINE Kinase Signal Transduction
• 年，卷（期）: 2013,（3）
• 页码范围: 23-33
• 页数: 11页
• 分类号: R73

摘要

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.