The C-terminal SH3 domain of the adapter protein Grb2 binds with high affinity to sequences in Gab1 and SLP-76 which lack the SH3-typical P-x-x-P core motif

Oncogene
Marc LewitzkyStephan M Feller

Abstract

The adapter Grb2 is an important mediator of normal cell proliferation and oncogenic signal transduction events. It consists of a central SH2 domain flanked by two SH3 domains. While the binding specificities of the Grb2 SH2 and N-terminal SH3 domain [Grb2 SH3(N)] have been studied in detail, binding properties of the Grb2 SH3(C) domain remained poorly defined. Gab1, a receptor tyrosine kinase substrate which associates with Grb2 and the c-Met receptor, was previously shown to bind Grb2 via a region which lacks a Grb2 SH3(N)-typical motif (P-x-x-P-x-R). Precipitation experiments with the domains of Grb2 show now that Gab1 can bind stably to the Grb2 SH3(C) domain. For further analyses, Gab1 mutants were generated by PCR to test in vivo residues thought to be crucial for Grb2 SH3(C) binding. The Grb2 SH3(C) binding region of Gab1 has significant homology to a region of the adapter protein SLP-76. Peptides corresponding to epitopes SLP-76, Gab1, SoS and other proteins with related sequences, as well as mutant peptides were synthesized and analysed by tryptophan-fluorescence spectrometry and by in vitro competition experiments. These experiments define a 13 amino acid sequence with the unusual consensus motif P-x-x-x-R-x-x-K-P as ...Continue Reading

References

Jul 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·D BowtellP Senior
Nov 1, 1991·Proceedings of the National Academy of Sciences of the United States of America·C T ChienS Fields
Sep 1, 1995·Nature Structural Biology·A P EijkelenboomK Hård
Aug 1, 1995·FEBS Letters·P ChardinA Ducruix
Mar 31, 1995·The Journal of Biological Chemistry·J K JackmanP R Findell
Feb 20, 1996·Proceedings of the National Academy of Sciences of the United States of America·A B SparksB K Kay
May 24, 1996·The Journal of Biological Chemistry·G S FengJ Ni
Apr 1, 1997·Current Opinion in Cell Biology·M J Robinson, M H Cobb
Dec 24, 1997·Current Topics in Microbiology and Immunology·T TakenawaK Matuoka
May 6, 1998·Oncogene·X X XuJ D Lambeth
Aug 8, 1998·The Journal of Biological Chemistry·K Okkenhaug, R Rottapel
Jan 5, 1999·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·D CussacC Garbay

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Citations

Dec 17, 2009·Archives of Biochemistry and Biophysics·Caleb B McDonaldAmjad Farooq
Aug 26, 2010·The Journal of Biological Chemistry·Ilana BerlinPiers D Nash
Nov 25, 2005·Stem Cells and Development·Gurudutta U GangenahalliPratibha M Luthra
Oct 21, 2010·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Rui ZengGang Xu
Aug 15, 2012·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Bernard A Liu, Piers D Nash
Mar 3, 2006·Acta Crystallographica. Section F, Structural Biology and Crystallization Communications·Alessandro Faravelli, Nazzareno Dimasi
Mar 18, 2003·Molecular and Cellular Biology·Sho YamasakiTakashi Saito
Sep 10, 2009·Cell Communication and Signaling : CCS·Franziska U WöhrleTilman Brummer
Apr 12, 2002·FEBS Letters·Yan Liu, Larry R Rohrschneider
Mar 31, 2015·FEBS Letters·Silvia Wuertenberger, Yvonne Groemping
Apr 20, 2004·FEBS Letters·Hye Jin LeeJungho Kim
Apr 30, 2008·Archives of Biochemistry and Biophysics·Caleb B McDonaldAmjad Farooq
Dec 5, 2006·Journal of Molecular Biology·Holger SchmidtDieter Willbold
Nov 17, 2009·Immunological Reviews·Konstantin NeumannJürgen Wienands
Apr 10, 2009·Molecular Systems Biology·Nikolay BorisovBoris N Kholodenko
Jan 22, 2013·Journal of Molecular Recognition : JMR·Caleb B McDonaldAmjad Farooq
Apr 22, 2005·Journal of Molecular Biology·Katja HeuerChristian Freund
Nov 26, 2005·Biochemical and Biophysical Research Communications·Xiaofeng LiZihe Rao
Jul 13, 2011·Biochimica Et Biophysica Acta·Slava RomFrancesca Peruzzi
Jun 16, 2009·Structure·Franziska U WöhrleTilman Brummer
Apr 18, 2014·Biophysical Journal·James M KriegerAlfonso De Simone

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