Gab1 acts as an adapter molecule linking the cytokine receptor gp130 to ERK mitogen-activated protein kinase.

Molecular and Cellular Biology
M Takahashi-TezukaT Hirano

Abstract

Gab1 has structural similarities with Drosophila DOS (daughter of sevenless), which is a substrate of the protein tyrosine phosphatase Corkscrew. Both Gab1 and DOS have a pleckstrin homology domain and tyrosine residues, potential binding sites for various SH2 domain-containing adapter molecules when they are phosphorylated. We found that Gab1 was tyrosine phosphorylated in response to various cytokines, such as interleukin-6 (IL-6), IL-3, alpha interferon (IFN-alpha), and IFN-gamma. Upon the stimulation of IL-6 or IL-3, Gab1 was found to form a complex with phosphatidylinositol (PI)-3 kinase and SHP-2, a homolog of Corkscrew. Mutational analysis of gp130, the common subunit of IL-6 family cytokine receptors, revealed that neither tyrosine residues of gp130 nor its carboxy terminus was required for tyrosine phosphorylation of Gab1. Expression of Gab1 enhanced gp130-dependent mitogen-activated protein (MAP) kinase ERK2 activation. A mutation of tyrosine 759, the SHP-2 binding site of gp130, abrogated the interactions of Gab1 with SHP-2 and PI-3 kinase as well as ERK2 activation. Furthermore, ERK2 activation was inhibited by a dominant negative p85 PI-3 kinase, wortmannin, or a dominant negative Ras. These observations suggest th...Continue Reading

References

Oct 19, 1995·Nature·J N Ihle
Jul 19, 1994·Proceedings of the National Academy of Sciences of the United States of America·A M BennettB G Neel
Mar 1, 1996·Molecular and Cellular Biology·A M BennettB G Neel
Jan 1, 1996·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·M HibiT Hirano
Dec 13, 1996·Biochemical and Biophysical Research Communications·N OkadaS Koizumi
Nov 14, 1997·Proceedings of the National Academy of Sciences of the United States of America·M Holgado-MadrugaA J Wong
Mar 20, 1998·International Reviews of Immunology·T Hirano

❮ Previous
Next ❯

Citations

Sep 20, 2000·The Journal of Cell Biology·M SachsW Birchmeier
Sep 21, 2012·Expert Opinion on Investigational Drugs·Raoul TibesRuben A Mesa
Jun 28, 2000·The Journal of Cell Biology·U SchaeperW Birchmeier
Feb 26, 2016·Cytokine·Jean-Christophe Beltra, Hélène Decaluwe
Jan 1, 2013·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Toshiki OguroYoshiyuki Kojima
Mar 10, 2004·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Natsuko HigashiKoichi Nakajima
May 28, 2010·Journal of Cellular Biochemistry·Angelina FeliciDonald P Bottaro
Dec 19, 2015·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Kunimaro FurutaTetsuo Takehara
Feb 1, 2005·Biochimica Et Biophysica Acta·Kazuya Machida, Bruce J Mayer
Mar 5, 2002·American Journal of Human Genetics·Kristin A Waite, Charis Eng
Jul 21, 2015·Cytokine & Growth Factor Reviews·Fred Schaper, Stefan Rose-John
Oct 26, 2011·Brain Research Bulletin·Joshua A SmithNaren L Banik
Feb 22, 2002·Experimental Cell Research·Jan Jacob SchuringaWiebe Kruijer
Jan 27, 2015·Trends in Immunology·Jan MauerJens C Brüning
Mar 13, 1999·Current Biology : CB·G Huyer, D R Alexander
Dec 6, 2011·European Journal of Cell Biology·René EulenfeldFred Schaper
Apr 13, 2000·The European Journal of Neuroscience·G D'ArcangeloF Benfenati
Jan 5, 2012·Advances in Hematology·Sheetal VermaKevin D Bunting
Mar 30, 2007·Mediators of Inflammation·Cheng-Ping HuMing-En Yu
Mar 7, 2003·Human Molecular Genetics·Kristin A Waite, Charis Eng
Mar 11, 2010·International Immunology·Chika KitabayashiToshio Hirano
Feb 20, 2004·The Journal of Biological Chemistry·Anders KallinCarl-Henrik Heldin
Sep 5, 2003·International Journal of Hematology·Hideaki IshikawaMichio M Kawano

❮ Previous
Next ❯

Related Concepts

Related Feeds

AKT Pathway

This feed focuses on the AKT serine/threonine kinase, which is an important signaling pathway involved in processes such as glucose metabolism and cell survival.