Specificity of the PTB domain of Shc for beta turn-forming pentapeptide motifs amino-terminal to phosphotyrosine.

The Journal of Biological Chemistry
T TrübS E Shoelson

Abstract

Shc phosphorylation in cells following growth factor, insulin, cytokine, and lymphocyte receptor activation leads to its association with Grb2 and activation of Ras. In addition to being a cytoplasmic substrate of tyrosine kinases, Shc contains an SH2 domain and a non-SH2 phosphotyrosine binding (PTB) domain. Here we show that the Shc PTB domain, but not the SH2 domain, binds with high affinity (ID50 approximately equal to 1 microM) to phosphopeptides corresponding to the sequence surrounding Tyr250 of the polyoma virus middle T (mT) antigen (LLSNPTpYSVMRSK). Truncation studies show that five residues amino-terminal to tyrosine are required for high affinity binding, whereas all residues carboxyl-terminal to tyrosine can be deleted without loss of affinity. Substitution studies show that tyrosine phosphorylation is required and residues at -5, -3, -2, and -1 positions relative to pTyr are important for this interaction. 1H NMR studies demonstrate that the phosphorylated mT antigen-derived sequence forms a stable beta turn in solution, and correlations between structure and function indicate that the beta turn is important for PTB domain recognition. These results show that PTB domains are functionally distinct from SH2 domains....Continue Reading

References

Jan 1, 1978·Annual Review of Biochemistry·P Y Chou, G D Fasman
Aug 1, 1994·Molecular and Cellular Biology·A G BatzerJ Schlessinger
Dec 16, 1994·Science·W M Kavanaugh, L T Williams
Mar 12, 1993·Cell·Z SongyangR J Lechleider
Jul 5, 1994·Proceedings of the National Academy of Sciences of the United States of America·K S CampbellD C Pallas

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Citations

Mar 26, 2002·FEBS Letters·Kelley S YanMing Ming Zhou
Jun 4, 1999·Progress in Biophysics and Molecular Biology·Z Songyang
Sep 7, 2001·Current Opinion in Cell Biology·D R PhillipsL Nannizzi-Alaimo
Nov 7, 2002·Bioorganic & Medicinal Chemistry Letters·Kyeong LeeTerrence R Burke
Aug 26, 1999·Trends in Endocrinology and Metabolism : TEM·B Margolis
Aug 1, 1997·Current Opinion in Chemical Biology·S E Shoelson
Apr 1, 1996·Nature Structural Biology·M M ZhouS W Fesik
Apr 19, 2000·The Biochemical Journal·A V OleinikovS P Makker
Mar 26, 1999·European Journal of Biochemistry·C Wellbrock, M Schartl
May 28, 1996·Proceedings of the National Academy of Sciences of the United States of America·K S RavichandranS J Burakoff
Feb 20, 1996·Proceedings of the National Academy of Sciences of the United States of America·J E DamenG Krystal
May 25, 1999·Inflammatory Bowel Diseases·N J Boerth, G A Koretzky
Jan 25, 2008·Journal of Virology·Melissa S MaginnisTerence S Dermody
Mar 16, 2005·Molecular and Cellular Biology·Masahiro NishiSteven E Shoelson
Jun 8, 1999·Annual Review of Immunology·K NelmsW E Paul
Jul 22, 1997·Proceedings of the National Academy of Sciences of the United States of America·R BronsonT Benjamin
Feb 28, 2003·Proceedings of the National Academy of Sciences of the United States of America·David A CalderwoodMark H Ginsberg
Apr 1, 1996·Neurochemical Research·J Eichberg, S Iyer
Jul 17, 2003·Science's STKE : Signal Transduction Knowledge Environment·Joseph Schlessinger, Mark A Lemmon
May 8, 2002·Nature Reviews. Molecular Cell Biology·Michael B Yaffe
Dec 14, 1999·The Journal of Biological Chemistry·B RoshanL G Cantley
Dec 13, 1996·The Journal of Biological Chemistry·S C LiT Pawson
Dec 14, 2001·The Journal of Biological Chemistry·David D ChangTimothy A Springer
Jun 27, 2003·The Journal of Biological Chemistry·Mikyung YunHee-Won Park
Apr 7, 1998·Molecular and Cellular Biology·K DurickS S Taylor

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