BCR/ABL and IL-3 activate Rap1 to stimulate the B-Raf/MEK/Erk and Akt signaling pathways and to regulate proliferation, apoptosis, and adhesion

Oncogene
Aishun JinOsamu Miura

Abstract

The Ras family small GTPase Rap1 is activated by hematopoietic cytokines, such as interleukin (IL)-3, to induce beta1 integrin-mediated cell adhesion or by the BCR/ABL fusion tyrosine kinase to stimulate the MEK/Erk signaling pathway. Here, we demonstrate that the abrogation of Rap1 activation by SPA-1, a Rap1-specific GAP, inhibits activation of B-Raf, MEK, Erk, and Akt in a murine hematopoietic cell line, Ton.B210, stimulated with IL-3 or inducibly expressing BCR/ABL. Furthermore, Rap1 inactivation had an inhibitory effects on proliferation and survival of Ton.B210 cells, which were more remarkable when cells were stimulated by BCR/ABL than by IL-3. Induction of BCR/ABL expression increased adhesion of Ton.B210 cells to fibronectin in a manner at least partly dependent on its kinase activity, and Rap1 inhibition by SPA-1 partially inhibited BCR/ABL-induced adhesion of cells. Thus, IL-3- or BCR/ABL-induced activation of Rap1 may play important roles in regulation of cell proliferation and survival through activation of the B-Raf/MEK/Erk and Akt signaling pathways and in induction of integrin-mediated cell adhesion. Furthermore, as compared with IL-3, BCR/ABL is more dependent on Rap1-mediated signaling to induce cell prolifera...Continue Reading

References

Aug 11, 1988·Nucleic Acids Research·V PizonA Tavitian
Oct 19, 1995·Nature·J N Ihle
Jan 1, 1994·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·S CulineB Olofsson
Jul 15, 1996·The Journal of Clinical Investigation·G BazzoniM E Hemler
Jan 1, 1997·Advances in Second Messenger and Phosphoprotein Research·J Downward
Mar 28, 1998·Current Biology : CB·A Denouel-GalyA Eychène
Mar 3, 1999·Proceedings of the National Academy of Sciences of the United States of America·A KrämerR Hehlmann
Jun 22, 1999·The Journal of Biological Chemistry·N TsukamotoN Minato
Jul 15, 1999·The New England Journal of Medicine·S FaderlH M Kantarjian
Oct 24, 2000·Oncogene·C BondziG W Krystal
Nov 1, 2000·Cell·D Bar-Sagi, A Hall
Jan 12, 2001·Physiological Reviews·Y TakaiT Matozaki
Mar 10, 2001·Molecular and Cellular Biology·O M TsygankovaJ L Meinkoth
May 2, 2001·Nature Reviews. Molecular Cell Biology·J L BosK A Reedquist
May 16, 2002·Blood·Jason A WertheimWarren S Pear
Jun 29, 2002·The Journal of Biological Chemistry·Liguang LouDaniel L Altschuler
May 27, 2003·Trends in Biochemical Sciences·Philip J S Stork
Oct 10, 2003·The New England Journal of Medicine·John M Goldman, Junia V Melo
Nov 11, 2003·Journal of Biochemistry·Masakazu Hattori, Nagahiro Minato
May 8, 2004·Trends in Biochemical Sciences·Derek P BrazilBrian A Hemmings
Aug 18, 2004·Trends in Molecular Medicine·Kohei KometaniNagahiro Minato
Nov 3, 2004·Nature Reviews. Molecular Cell Biology·Claudia WellbrockRichard Marais
Dec 15, 2004·Biochemical and Biophysical Research Communications·Daisuke MizuchiOsamu Miura
Jun 21, 2005·Nature Reviews. Cancer·Shoshana KleinAlexander Levitzki

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Citations

Jun 27, 2007·Immunology and Cell Biology·Huiyun ZhangShaoheng He
Aug 25, 2010·The Journal of Experimental Medicine·Aradhana AwasthiSubramaniam Malarkannan
Feb 9, 2011·Leukemia & Lymphoma·Amanda J RedigLeonidas C Platanias
Apr 15, 2010·Cellular Signalling·Manuela ManciniMaria Alessandra Santucci
May 6, 2008·Biochemical Pharmacology·Yun-Bin YeMichel Vidal
Oct 22, 2008·Molecular Reproduction and Development·Evanthia AivatiadouGiovanna Berruti
Nov 29, 2008·Cancer Science·Nagahiro Minato, Masakazu Hattori
May 29, 2016·Chinese Journal of Cancer·Zhi-Jie KangQuentin Liu
Feb 20, 2018·Critical Reviews in Biochemistry and Molecular Biology·Saeideh Nakhaei-RadMohammad Reza Ahmadian
Apr 21, 2016·Otolaryngology--head and Neck Surgery : Official Journal of American Academy of Otolaryngology-Head and Neck Surgery·Alok R KhandelwalCherie-Ann O Nathan
Aug 21, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Haiyan ChuSubramaniam Malarkannan
Sep 4, 2020·International Journal of Molecular Sciences·Alazne Arrazola SastreJosé Luis Zugaza
Jul 20, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Girija DasmahapatraSteven Grant

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