Literature DB >> 19345670

The juxtamembrane domain in ETV6/FLT3 is critical for PIM-1 up-regulation and cell proliferation.

Hoang Anh Vu1, Phan Thi Xinh, Yasuhiko Kano, Katsushi Tokunaga, Yuko Sato.   

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.

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Year:  2009        PMID: 19345670     DOI: 10.1016/j.bbrc.2009.03.157

Source DB:  PubMed          Journal:  Biochem Biophys Res Commun        ISSN: 0006-291X            Impact factor:   3.575


  6 in total

1.  ETV6-FLT3 fusion gene-positive, eosinophilia-associated myeloproliferative neoplasm successfully treated with sorafenib and allogeneic stem cell transplant.

Authors:  L Falchi; M Mehrotra; K J Newberry; L M Lyle; G Lu; K P Patel; R Luthra; U Popat; S Verstovsek
Journal:  Leukemia       Date:  2014-05-23       Impact factor: 11.528

2.  Adaptor protein Lnk binds to and inhibits normal and leukemic FLT3.

Authors:  De-Chen Lin; Tong Yin; Maya Koren-Michowitz; Ling-Wen Ding; Saskia Gueller; Sigal Gery; Takayuki Tabayashi; Ulla Bergholz; Julhash U Kazi; Lars Rönnstrand; Carol Stocking; H Phillip Koeffler
Journal:  Blood       Date:  2012-08-31       Impact factor: 22.113

3.  MicroRNA-16 is down-regulated in mutated FLT3 expressing murine myeloid FDC-P1 cells and interacts with Pim-1.

Authors:  Kyu-Tae Kim; Adam P Carroll; Baratali Mashkani; Murray J Cairns; Donald Small; Rodney J Scott
Journal:  PLoS One       Date:  2012-09-06       Impact factor: 3.240

Review 4.  Tyrosine kinase gene fusions in cancer: translating mechanisms into targeted therapies.

Authors:  Sandrine Medves; Jean-Baptiste Demoulin
Journal:  J Cell Mol Med       Date:  2012-02       Impact factor: 5.310

Review 5.  Pim kinases in hematological malignancies: where are we now and where are we going?

Authors:  Patrizia Mondello; Salvatore Cuzzocrea; Michael Mian
Journal:  J Hematol Oncol       Date:  2014-12-10       Impact factor: 17.388

6.  ETV6/FLT3 Fusion Is a Novel Client Protein of Hsp90.

Authors:  Bui Thi Kim Ly; Hoang Thanh Chi
Journal:  Oncol Res       Date:  2018-02-22       Impact factor: 5.574

  6 in total

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