title: The SH2 domain interaction landscape.
abstract: Members of the SH2 domain family modulate signal transduction by binding to short peptides containing phosphorylated tyrosines. Each domain displays a distinct preference for the sequence context of the phosphorylated residue. We have developed a high-density peptide chip technology that allows for probing of the affinity of most SH2 domains for a large fraction of the entire complement of tyrosine phosphopeptides in the human proteome. Using this technique, we have experimentally identified thousands of putative SH2-peptide interactions for more than 70 different SH2 domains. By integrating this rich data set with orthogonal context-specific information, we have assembled an SH2-mediated probabilistic interaction network, which we make available as a community resource in the PepspotDB database. A predicted dynamic interaction between the SH2 domains of the tyrosine phosphatase SHP2 and the phosphorylated tyrosine in the extracellular signal-regulated kinase activation loop was validated by experiments in living cells.
authors.affiliation: Department of Biology, University of Rome Tor Vergata, I-00133 Rome, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Tinti
authors.forename: Lars
authors.initials: L
authors.lastname: Kiemer
authors.forename: Stefano
authors.initials: S
authors.lastname: Costa
authors.forename: Martin L
authors.initials: ML
authors.lastname: Miller
authors.forename: Francesca
authors.initials: F
authors.lastname: Sacco
authors.forename: Jesper V
authors.initials: JV
authors.lastname: Olsen
authors.forename: Martina
authors.initials: M
authors.lastname: Carducci
authors.forename: Serena
authors.initials: S
authors.lastname: Paoluzi
authors.forename: Francesca
authors.initials: F
authors.lastname: Langone
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Workman
authors.forename: Nikolaj
authors.initials: N
authors.lastname: Blom
authors.forename: Kazuya
authors.initials: K
authors.lastname: Machida
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Thompson
authors.forename: Mike
authors.initials: M
authors.lastname: Schutkowski
authors.forename: Søren
authors.initials: S
authors.lastname: Brunak
authors.forename: Matthias
authors.initials: M
authors.lastname: Mann
authors.forename: Bruce J
authors.initials: BJ
authors.lastname: Mayer
authors.forename: Luisa
authors.initials: L
authors.lastname: Castagnoli
authors.forename: Gianni
authors.initials: G
authors.lastname: Cesareni
mesh_terms: D000595:Amino Acid Sequence; D002851:Chromatography, High Pressure Liquid; D030562:Databases, Protein; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D010748:Phosphopeptides / Q000737:chemistry* / Q000378:metabolism; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D040081:Protein Array Analysis; D060066:Protein Interaction Maps; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Q000737:chemistry / Q000378:metabolism; D020543:Proteome; D012372:ROC Curve; D053719:Tandem Mass Spectrometry; D018909:src Homology Domains
chemical_list: D010748:Phosphopeptides; D020543:Proteome; D019000:Phosphotyrosine; D048049:Extracellular Signal-Regulated MAP Kinases; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11
references.citation: BMC Bioinformatics. 2005 Dec 01;6 Suppl 4:S21
references.pmid: 16351748
references.citation: Mol Cell Proteomics. 2008 Apr;7(4):768-84
references.pmid: 17956856
references.citation: Trends Biotechnol. 2007 Oct;25(10):448-54
references.pmid: 17825444
references.citation: Nucleic Acids Res. 2008 Jan;36(Database issue):D679-83
references.pmid: 18160410
references.citation: Nature. 2006 Jan 12;439(7073):168-74
references.pmid: 16273093
references.citation: Biopolymers. 2000;55(3):188-206
references.pmid: 11074414
references.citation: Proc Natl Acad Sci U S A. 2004 Apr 20;101(16):6062-7
references.pmid: 15075390
references.citation: Proteomics. 2004 Jun;4(6):1551-61
references.pmid: 15174125
references.citation: Nucleic Acids Res. 2010 Jan;38(Database issue):D532-9
references.pmid: 19897547
references.citation: Trends Biochem Sci. 2008 Jun;33(6):241-2; author reply 242-3
references.pmid: 18472267
references.citation: Sci Signal. 2008 Sep 02;1(35):ra2
references.pmid: 18765831
references.citation: Nat Biotechnol. 2004 Feb;22(2):177-83
references.pmid: 14755292
references.citation: Mol Cell Proteomics. 2009 Mar;8(3):519-34
references.pmid: 19001411
references.citation: Nature. 1994 Jun 9;369(6480):502-5
references.pmid: 7515480
references.citation: Bioinformatics. 2006 Jul 1;22(13):1658-9
references.pmid: 16731699
references.citation: Mol Cell. 2007 Jun 22;26(6):899-915
references.pmid: 17588523
references.citation: Science. 1990 Nov 16;250(4983):979-82
references.pmid: 2173144
references.citation: Cell. 2004 Jan 23;116(2):191-203
references.pmid: 14744431
references.citation: Mol Syst Biol. 2005;1:2005.0008
references.pmid: 16729043
references.citation: Mol Cell Proteomics. 2010 Nov;9(11):2391-404
references.pmid: 20627867
references.citation: Nucleic Acids Res. 2007 Jan;35(Database issue):D572-4
references.pmid: 17135203
references.citation: Protein Sci. 2003 May;12(5):1007-17
references.pmid: 12717023
references.citation: Proc Natl Acad Sci U S A. 1990 Nov;87(21):8622-6
references.pmid: 2236073
references.citation: Nat Biotechnol. 2008 Dec;26(12):1367-72
references.pmid: 19029910
references.citation: J Mol Biol. 1999 Dec 17;294(5):1351-62
references.pmid: 10600390
references.citation: Drug Discov Today. 2005 Aug 15;10(16):1111-7
references.pmid: 16182196
references.citation: Nucleic Acids Res. 2010 Jul;38(Web Server issue):W35-40
references.pmid: 20525785
references.citation: Nat Rev Mol Cell Biol. 2002 Mar;3(3):177-86
references.pmid: 11994738
references.citation: Nature. 1996 Feb 8;379(6565):560-4
references.pmid: 8596638
references.citation: J Biol Chem. 2002 Jun 14;277(24):21666-74
references.pmid: 11929862
references.citation: Bioinformatics. 2005 Aug 15;21(16):3433-4
references.pmid: 15955779
references.citation: Nucleic Acids Res. 2012 Jan;40(Database issue):D857-61
references.pmid: 22096227
references.citation: Genome Biol. 2007;8(3):R39
references.pmid: 17367534
references.citation: Cell. 2006 Nov 3;127(3):635-48
references.pmid: 17081983
references.citation: Sci Signal. 2009 Sep 08;2(87):ra50
references.pmid: 19738200
references.citation: Nucleic Acids Res. 2008 Jan;36(Database issue):D240-4
references.pmid: 17962309
references.citation: Nat Methods. 2009 May;6(5):359-62
references.pmid: 19377485
references.citation: Cell. 2007 Jun 29;129(7):1415-26
references.pmid: 17570479
references.citation: Cell. 1993 Mar 12;72(5):767-78
references.pmid: 7680959
references.citation: Mol Cell. 2006 Jun 23;22(6):851-868
references.pmid: 16793553
references.citation: Nat Biotechnol. 2004 Sep;22(9):1139-45
references.pmid: 15314609
references.citation: Mol Syst Biol. 2011 Apr 26;7:484
references.pmid: 21525870