Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 292, Issue 12, Pages 4942-4952Publisher
ELSEVIER
DOI: 10.1074/jbc.M116.757518
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Funding
- DEPTH project of the European Research Council [322749]
- Italian Association for Cancer Research [14135]
- Telethon Grant [GGP09243]
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Reversible tyrosine phosphorylation is a widespread post-translational modification mechanism underlying cell physiology. Thus, understanding the mechanisms responsible for substrate selection by kinases and phosphatases is central to our ability to model signal transduction at a system level. Classical protein- tyrosine phosphatases can exhibit substrate specificity in vivo by combining intrinsic enzymatic specificity with the network of protein-protein interactions, which positions the enzymes in close proximity to their substrates. Here we use a high throughput approach, based on high density phosphopep-tide chips, to determine the in vitro substrate preference of 16 members of the protein-tyrosine phosphatase family. This approach helped identify one residue in the substrate binding pocket of the phosphatase domain that confers specificity for phosphopeptides in a specific sequence context. We also present a Bayesian model that combines intrinsic enzymatic specificity and interaction information in the context of the human protein interaction network to infer new phosphatase substrates at the proteome level.
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