Department of Biology, University of Rome Tor Vergata, I-00133 Rome, Italy
Lars Kiemer
Department of Biology, University of Rome Tor Vergata, I-00133 Rome, Italy
Stefano Costa
Department of Biology, University of Rome Tor Vergata, I-00133 Rome, Italy
Martin L. Miller
Center for Biological Sequence Analysis, Technical University of Denmark, DK-2800 Lyngby, Denmark
Francesca Sacco
Department of Biology, University of Rome Tor Vergata, I-00133 Rome, Italy
Jesper V. Olsen
Department of Proteomics and Signal Transduction, Max-Planck Institute for Biochemistry, Am Klopferspitz 18, D-82152 Martinsried, Germany
Martina Carducci
Department of Biology, University of Rome Tor Vergata, I-00133 Rome, Italy
Serena Paoluzi
Department of Biology, University of Rome Tor Vergata, I-00133 Rome, Italy
Francesca Langone
Department of Biology, University of Rome Tor Vergata, I-00133 Rome, Italy
Christopher T. Workman
Center for Biological Sequence Analysis, Technical University of Denmark, DK-2800 Lyngby, Denmark
Nikolaj Blom
Center for Biological Sequence Analysis, Technical University of Denmark, DK-2800 Lyngby, Denmark
Kazuya Machida
Department of Genetics and Developmental Biology, Raymond and Beverly Sackler Laboratory of Genetics and Molecular Medicine, University of Connecticut Health Center, Farmington, CT 06030, USA
Christopher M. Thompson
Department of Genetics and Developmental Biology, Raymond and Beverly Sackler Laboratory of Genetics and Molecular Medicine, University of Connecticut Health Center, Farmington, CT 06030, USA
Center for Biological Sequence Analysis, Technical University of Denmark, DK-2800 Lyngby, Denmark
Matthias Mann
Department of Proteomics and Signal Transduction, Max-Planck Institute for Biochemistry, Am Klopferspitz 18, D-82152 Martinsried, Germany
Bruce J. Mayer
Department of Genetics and Developmental Biology, Raymond and Beverly Sackler Laboratory of Genetics and Molecular Medicine, University of Connecticut Health Center, Farmington, CT 06030, USA
Luisa Castagnoli
Department of Biology, University of Rome Tor Vergata, I-00133 Rome, Italy
Gianni Cesareni
Department of Biology, University of Rome Tor Vergata, I-00133 Rome, Italy
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.
