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Sci. Signal., 2 September 2008
Vol. 1, Issue 35, p. ra2
[DOI: 10.1126/scisignal.1159433]

RESEARCH ARTICLES

Linear Motif Atlas for Phosphorylation-Dependent Signaling

Martin Lee Miller 1 , 2 *, Lars Juhl Jensen 2 , 3 *, Francesca Diella 3 , Claus Jørgensen 4 , Michele Tinti 5 , Lei Li 6 , Marilyn Hsiung 4 , Sirlester A. Parker 7 , Jennifer Bordeaux 7 , Thomas Sicheritz-Ponten 1 , Marina Olhovsky 4 , Adrian Pasculescu 4 , Jes Alexander 8 , Stefan Knapp 9 , Nikolaj Blom 1 , Peer Bork 2 , 10 , Shawn Li 6 , Gianni Cesareni 5 , Tony Pawson 4 , Benjamin E. Turk 7 , Michael B. Yaffe 8 {dagger} , Søren Brunak 1 , 2 {dagger} , and Rune Linding 4 , 8 , 11 {dagger}

1 Center for Biological Sequence Analysis, Technical University of Denmark, 2800 Lyngby, Denmark.
2 The Novo Nordisk Foundation Centre for Protein Research, University of Copenhagen, 2200 Copenhagen, Denmark.
3 European Molecular Biology Laboratory, 69117 Heidelberg, Germany.
4 Samuel Lunenfeld Research Institute, Mount Sinai Hospital, M5G 1X5 Toronto, Ontario, Canada.
5 University of Rome, Tor Vergata, 00133 Rome, Italy.
6 University of Western Ontario, N6A 5C1 London, Ontario, Canada.
7 Department of Pharmacology, Yale University School of Medicine, New Haven, 06520 CT, USA.
8 Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, 021329 MA, USA.
9 Structural Genomics Consortium, University of Oxford, OX3 7DQ Oxford, UK.
10 Max-Delbrück-Centre for Molecular Medicine, 13092 Berlin, Germany.
11 Cellular & Molecular Logic Team, The Institute of Cancer Research, SW3 6JB London, UK.

* These authors contributed equally to this work.

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).

{dagger} To whom correspondence should be addressed. E-mail: brunak{at}cbs.dtu.dk (S.B.), myaffe{at}mit.edu (M.B.Y.), and rune.linding{at}gmail.com (R.L.)

Citation: M. L. Miller, L. J. Jensen, F. Diella, C. Jørgensen, M. Tinti, L. Li, M. Hsiung, S. A. Parker, J. Bordeaux, T. Sicheritz-Ponten, M. Olhovsky, A. Pasculescu, J. Alexander, S. Knapp, N. Blom, P. Bork, S. Li, G. Cesareni, T. Pawson, B. E. Turk, M. B. Yaffe, S. Brunak, R. Linding, Linear Motif Atlas for Phosphorylation-Dependent Signaling. Sci. Signal. 1, ra2 (2008).

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