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The juxtamembrane domain in ETV6/FLT3 is critical for PIM-1 up-regulation and cell proliferation |
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| Authors: | Hoang Anh Vu Phan Thi Xinh Katsushi Tokunaga |
| Institution: | a Consolidated Research Institute for Advanced Science and Medical Care (ASMeW), Waseda University, Tokyo, Japan b Division of Ultrafine Structure, Department of Pathology, Research Institute of International Medical Center of Japan, Toyama 1-21-1, Shinjuku-ku, Tokyo 162-8655, Japan c Department of Human Genetics, School of International Health, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan d Division of Hematology, Department of Hematology and Medical Oncology, Tochigi Cancer Center, Tochigi, Japan |
| Abstract: | 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. |
| Keywords: | ETV6/FLT3 PIM-1 STAT5 MAPK AKT |
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