Vu Hoang Anh, Xinh Phan Thi, Kano Yasuhiko, Tokunaga Katsushi, Sato Yuko
Consolidated Research Institute for Advanced Science and Medical Care, Waseda University, Tokyo, Japan.
Biochem Biophys Res Commun. 2009 Jun 5;383(3):308-13. doi: 10.1016/j.bbrc.2009.03.157. Epub 2009 Apr 5.
We recently reported that the ETV6/FLT3 fusion protein conferred interleukin-3-independent growth on Ba/F3 cells. The present study has been conducted to assess role of the juxtamembrane domain of FLT3 for signal transduction and cell transformation. The wild-type ETV6/FLT3 fusion protein in transfected cells was a constitutively activated tyrosine kinase that led to up-regulation of PIM-1 and activations of STAT5, AKT, and MAPK. Deletion of the juxtamembrane domain abrogated interleukin-3-independent growth of the transfected cells and PIM-1 up-regulation, whereas it retained compatible levels of phosphorylations of STAT5, AKT, and MAPK. Further deletion of N-terminal region of the tyrosine kinase I domain of FLT3 completely abolished these phosphorylations. Our data indicate that the juxtamembrane domain of FLT3 in ETV6/FLT3 fusion protein is critical for cell proliferation and PIM-1 up-regulation that might be independent of a requirement for signaling through STAT5, MAPK, and AKT pathways.
我们最近报道，ETV6/FLT3融合蛋白赋予Ba/F3细胞白细胞介素-3非依赖性生长特性。本研究旨在评估FLT3近膜结构域在信号转导和细胞转化中的作用。转染细胞中的野生型ETV6/FLT3融合蛋白是一种组成性激活的酪氨酸激酶，可导致PIM-1上调以及STAT5、AKT和MAPK激活。近膜结构域的缺失消除了转染细胞的白细胞介素-3非依赖性生长和PIM-1上调，而它保留了STAT5、AKT和MAPK的磷酸化水平。进一步缺失FLT3酪氨酸激酶I结构域的N端区域完全消除了这些磷酸化。我们的数据表明，ETV6/FLT3融合蛋白中FLT3的近膜结构域对于细胞增殖和PIM-1上调至关重要，这可能独立于通过STAT5、MAPK和AKT途径进行信号传导的需求。
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