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.
journal_name
Cell Systjournal_title
Cell systemsauthors
Corwin T,Woodsmith J,Apelt F,Fontaine JF,Meierhofer D,Helmuth J,Grossmann A,Andrade-Navarro MA,Ballif BA,Stelzl Udoi
10.1016/j.cels.2017.08.001subject
Has Abstractpub_date
2017-08-23 00:00:00pages
128-139.e4issue
2eissn
2405-4712issn
2405-4720pii
S2405-4712(17)30334-4journal_volume
5pub_type
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