The SH2 Domain Interaction Landscape

Michele Tinti, Lars Kiemer, Stefano Costa, Martin L. Miller, Francesca Sacco, Jesper V. Olsen, Martina Carducci, Serena Paoluzi, Francesca Langone, Christopher T. Workman, Nikolaj Blom, Kazuya Machida, Christopher M. Thompson, Mike Schutkowski, Søren Brunak, Matthias Mann, Bruce J. Mayer, Luisa Castagnoli, Gianni Cesareni

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)1293-1305
Number of pages13
JournalCell Reports
Issue number4
Publication statusPublished - Apr 25 2013

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


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