Phosphotyrosines 627 and 659 of Gab1 constitute a bisphosphoryl tyrosine-based activation motif (BTAM) conferring binding and activation of SHP2

The Journal of Biological Chemistry
J M CunnickJ Wu

Abstract

A major Grb2-associated binder-1 (Gab1) binding partner in epidermal growth factor (EGF)-stimulated cells is protein-tyrosine phosphatase (PTPase) SHP2, which contains tandem SH2 domains. The SHP2 PTPase activity is required for activation of the extracellular signal-regulated kinase (ERK) subfamily of mitogen-activated protein (MAP) kinase by EGF. To investigate the mechanism by which Gab1 and SHP2 mediate ERK activation, we characterized the Gab1-SHP2 interaction. We found that both Tyr-627 and Tyr-659 of Gab1 were required for SHP2 binding to Gab1 and for ERK2 activation by EGF. Far Western blot analysis suggested that the tandem SH2 domains of SHP2 bind to Gab1 in a specific orientation, in which the N-SH2 domain binds to phosphotyrosine (Tyr(P))-627 and the C-SH2 domain binds to Tyr(P)-659. When assayed with peptide substrates, SHP2 PTPase was activated by a bisphosphopeptide containing both Tyr(P)-627 and Tyr(P)-659, but not by monophosphopeptides containing Tyr(P)-627 or Tyr(P)-659 or a mixture of these monophosphopeptides. These results suggest that Tyr(P)-627 and Tyr(P)-659 of Gab1 constitute a bisphosphoryl tyrosine-based activation motif (BTAM) that binds and activates SHP2. Remarkably, while a constitutively active ...Continue Reading

References

Mar 1, 1982·Analytical Biochemistry·H HasegawaS Kaufman
Nov 8, 1994·Proceedings of the National Academy of Sciences of the United States of America·T FurukawaH Saito
Jul 21, 1995·The Journal of Biological Chemistry·B E HawesR J Lefkowitz
Mar 1, 1996·Molecular and Cellular Biology·A M BennettB G Neel
Apr 1, 1997·Current Opinion in Cell Biology·B G Neel, N K Tonks
Feb 14, 1998·The Journal of Biological Chemistry·E A OttingerS E Shoelson
Mar 10, 1998·Cell·P HofS E Shoelson
Aug 24, 1999·The Journal of Biological Chemistry·A WickremaL C Platanias
Dec 2, 1999·Experimental Cell Research·G S Feng

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Citations

May 15, 2002·Immunology Letters·Gábor KonczGabriella Sármay
Mar 12, 2003·Trends in Cell Biology·Haihua Gu, Benjamin G Neel
Jun 7, 2003·Trends in Cell Biology·Marta Rosário, Walter Birchmeier
Jun 27, 2003·Trends in Biochemical Sciences·Benjamin G NeelLily Pao
Dec 3, 2010·The Journal of Biological Chemistry·Emanuela FerrariLuisa Castagnoli
Jun 10, 2006·The Journal of Biological Chemistry·Ning WangZhizhuang Joe Zhao
Jul 31, 2010·Journal of Molecular Cell Biology·Songshu MengChuangui Wang
Jun 2, 2006·Molecular and Cellular Biology·Emilie A Bard-ChapeauGen-Sheng Feng
Mar 14, 2012·Molecular and Cellular Biology·Aurelio Pio NardozzaLuisa Castagnoli
Jan 30, 2004·Molecular and Cellular Biology·Yingqing SunGen-Sheng Feng
Mar 5, 2011·Arteriosclerosis, Thrombosis, and Vascular Biology·Jinjing ZhaoZheng Gen Jin
Sep 10, 2009·Cell Communication and Signaling : CCS·Franziska U WöhrleTilman Brummer
Jan 11, 2007·International Journal of Medical Sciences·Yasuyuki GotoNobuyuki Hamajima
Feb 1, 2014·Carcinogenesis·Valentina E SchneebergerJie Wu
Mar 5, 2013·The Journal of Biological Chemistry·Zhi-Hong YuZhong-Yin Zhang
Apr 25, 2013·The Journal of Biological Chemistry·Ying-Xin FanGibbes R Johnson
Aug 1, 2007·The Journal of Cell Biology·Marta RosárioWalter Birchmeier
Oct 9, 2002·The Journal of Cell Biology·Ti CaiPaul A Khavari
Sep 6, 2015·European Journal of Medical Genetics·Mylène TajanArmelle Yart
May 23, 2014·Journal of Cellular Biochemistry·Xiuqin NiJeffrey R Jacobson
Oct 25, 2011·Cellular Signalling·Ma Eugenia DíazDaniel Turyn
Mar 2, 2016·Proceedings of the National Academy of Sciences of the United States of America·Raven J ReddyForest M White
Jun 1, 2010·Biochemical Pharmacology·Liwei ChenJie Wu
Jun 18, 2014·Biochemistry·Zhi-Hong YuZhong-Yin Zhang
Dec 3, 2015·Scientific Reports·Chuan ChenDuqiang Luo
Apr 3, 2003·Immunological Reviews·Takashi Saito, Sho Yamasaki
Oct 15, 2013·Wiley Interdisciplinary Reviews. Systems Biology and Medicine·Lily A ChylekWilliam S Hlavacek
May 27, 2006·Biochemical and Biophysical Research Communications·Maya Gavrieli, Kenneth M Murphy
Jan 9, 2007·Biophysical Journal·Dipak BaruaJason M Haugh
Nov 30, 2012·Clinical Science·Lorna J Hale, Richard J M Coward
Feb 23, 2013·International Journal of Inflammation·Yoshikazu Nakaoka, Issei Komuro
May 15, 2015·Science Signaling·Christopher M FurchtMatthew J Lazzara
Oct 16, 2013·Biochimica Et Biophysica Acta·Monica AasrumThoralf Christoffersen

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