Linear motif atlas for phosphorylation-dependent signaling

Martin Lee Miller, Lars Juhl Jensen, Francesca Diella, Claus Jørgensen, Michele Tinti, Lei Li, Marilyn Hsiung, Sirlester A Parker, Jennifer Bordeaux, Thomas Sicheritz-Ponten, Marina Olhovsky, Adrian Pasculescu, Jes Alexander, Stefan Knapp, Nikolaj Blom, Peer Bork, Shawn Li, Gianni Cesareni, Tony Pawson, Benjamin E TurkMichael B Yaffe, Søren Brunak, Rune Linding

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385 Citations (Scopus)

Abstract

Systematic and quantitative analysis of protein phosphorylation is revealing dynamic regulatory networks underlying cellular responses to environmental cues. However, matching these sites to the kinases that phosphorylate them and the phosphorylation-dependent binding domains that may subsequently bind to them remains a challenge. NetPhorest is an atlas of consensus sequence motifs that covers 179 kinases and 104 phosphorylation-dependent binding domains [Src homology 2 (SH2), phosphotyrosine binding (PTB), BRCA1 C-terminal (BRCT), WW, and 14-3-3]. The atlas reveals new aspects of signaling systems, including the observation that tyrosine kinases mutated in cancer have lower specificity than their non-oncogenic relatives. The resource is maintained by an automated pipeline, which uses phylogenetic trees to structure the currently available in vivo and in vitro data to derive probabilistic sequence models of linear motifs. The atlas is available as a community resource (http://netphorest.info).
Original languageEnglish
JournalScience Signaling
Volume1
Issue number35
Pages (from-to)ra2
DOIs
Publication statusPublished - 2008

Keywords

  • 14-3-3 Proteins
  • Amino Acid Motifs
  • Animals
  • BRCA1 Protein
  • Consensus Sequence
  • Databases, Protein
  • Humans
  • Phosphorylation
  • Phosphotransferases
  • Phosphotyrosine
  • Protein Binding
  • Signal Transduction
  • src Homology Domains

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