Differential effect of leukaemogenic tyrosine kinases on cell motility is governed by subcellular localisation

British Journal of Haematology
A PierceE Spooncer

Abstract

The chemokine, stromal cell-derived factor-1 (SDF-1) is a crucial regulator of stem cell homing and tethering, and potentiation of this pathway in leukaemias may contribute to the pathogenesis of the disease. A key second messenger in SDF-1 signal/response coupling is phosphatidylinositol 3,4,5-triphosphate [PtdIns(3,4,5)P3]. SDF-1 elevated PtdIns(3,4,5)P3 levels markedly in the multipotent FDCP-mix stem cell line. Similarly, transfection with BCR/ABL or TEL/PDGFRbeta leukaemogenic tyrosine kinases chronically elevated PtdIns(3,4,5)P3 levels. However, whilst an SDF-1 chemotactic response was observed in TEL/PDGFRbeta-transfected cells, in BCR/ABL cells this was markedly decreased, which was not due to Ras-pathway activation. Thus, multipotent cells can respond to SDF-1, despite chronic increases in this second messenger indicating that a discrete pool of SDF-1-stimulated PtdIns(3,4,5)P3 production drives the chemotactic response. To discern the mechanism for the differential effects of these oncogenes we considered subcellular localisation. As TEL/PDGFRbeta has a cytosolic location whilst BCR/ABL associates with actin, we removed the actin-binding domain from BCR/ABL. We observed relocation of BCR/ABL to the cytosol and increas...Continue Reading

References

Nov 30, 1999·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·N L HarrisC D Bloomfield
Dec 22, 1999·The Journal of Clinical Investigation·C H KimH E Broxmeyer
Apr 26, 2001·Proceedings of the National Academy of Sciences of the United States of America·F C YangD A Williams
Dec 1, 2001·Science·D E WrightI L Weissman
Dec 26, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·Miguel Vicente-ManzanaresFrancisco Sánchez-Madrid
Sep 5, 2002·The Journal of Experimental Medicine·Andrzej PtasznikAlan M Gewirtz
Dec 12, 2002·Oncogene·Jason A WertheimWarren S Pear
Nov 19, 2003·Biochemical and Biophysical Research Communications·Reinhard HenschlerDietrich Möbest
Dec 22, 2004·The Journal of Biological Chemistry·Masato MoriguchiJohn J O'Shea
Feb 21, 2006·British Journal of Haematology·N Underhill-DayP J Owen-Lynch

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Citations

Jan 15, 2016·Journal of Controlled Release : Official Journal of the Controlled Release Society·Michael AnsorgeTilo Pompe
Aug 30, 2008·British Journal of Haematology·Drew ProvanRoberto Stasi
Jun 25, 2008·British Journal of Haematology·Bethan Psaila, James B Bussel
Oct 24, 2007·Molecular & Cellular Proteomics : MCP·Andrew PierceAnthony D Whetton
Sep 3, 2013·Molecular & Cellular Proteomics : MCP·Andrew J K WilliamsonAnthony D Whetton

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