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  Defining Human Tyrosine Kinase Phosphorylation Networks Using Yeast as an In Vivo Model Substrate

Corwin, T., Woodsmith, J., Apelt, F., Fontaine, J.-F., Meierhofer, D., Helmuth, J., et al. (2017). Defining Human Tyrosine Kinase Phosphorylation Networks Using Yeast as an In Vivo Model Substrate. Cell Systems, 5(2): e4, pp. 128-139. doi:10.1016/j.cels.2017.08.001.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-002D-D356-7 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-002D-D357-5
Genre: Journal Article

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 Creators:
Corwin, Thomas, Author
Woodsmith, Jonathan, Author
Apelt, Federico, Author
Fontaine, Jean-Fred , Author
Meierhofer, David1, Author              
Helmuth, Johannes, Author
Grossmann, Arndt, Author
Andrade-Navarro, Miguel A. , Author
Ballif, Bryan A. , Author
Stelzl, Ulrich, Author
Affiliations:
1Mass Spectrometry (Head: David Meierhofer), Scientific Service (Head: Christoph Krukenkamp), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479669              

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Free keywords: kinase-substrate specificity; network propagation; protein interaction networks; tyrosine phosphorylation
 Abstract: Systematic assessment of tyrosine kinase-substrate relationships is fundamental to a better understanding of cellular signaling and its profound alterations in human diseases such as cancer. In human cells, such assessments are confounded by complex signaling networks, feedback loops, conditional activity, and intra-kinase redundancy. Here we address this challenge by exploiting the yeast proteome as an in vivo model substrate. We individually expressed 16 human non-receptor tyrosine kinases (NRTKs) in Saccharomyces cerevisiae and identified 3,279 kinase-substrate relationships involving 1,351 yeast phosphotyrosine (pY) sites. Based on the yeast data without prior information, we generated a set of linear kinase motifs and assigned ∼1,300 known human pY sites to specific NRTKs. Furthermore, experimentally defined pY sites for each individual kinase were shown to cluster within the yeast interactome network irrespective of linear motif information. We therefore applied a network inference approach to predict kinase-substrate relationships for more than 3,500 human proteins, providing a resource to advance our understanding of kinase biology.

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Language(s): eng - English
 Dates: 2017-08-23
 Publication Status: Published online
 Pages: -
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 Table of Contents: -
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 Identifiers: DOI: 10.1016/j.cels.2017.08.001
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Title: Cell Systems
Source Genre: Journal
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Pages: - Volume / Issue: 5 (2) Sequence Number: e4 Start / End Page: 128 - 139 Identifier: -