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Updated: Jul 2, 2026

Identification of Kinase-substrate Pairs Using High Throughput Screening
Published on: August 29, 2015
Linear motif atlas for phosphorylation-dependent signaling
Martin Lee Miller1, Lars Juhl Jensen, Francesca Diella
1Center for Biological Sequence Analysis, Technical University of Denmark, 2800 Lyngby, Denmark.
NetPhorest is a new resource mapping protein phosphorylation sites to kinases and binding domains. This atlas reveals cancer-related tyrosine kinases have lower specificity, aiding cell signaling research.
Area of Science:
- Biochemistry
- Molecular Biology
- Bioinformatics
Background:
- Protein phosphorylation is crucial for cellular signaling networks.
- Identifying kinases and binding domains for phosphorylation sites is challenging.
Purpose of the Study:
- To create NetPhorest, an atlas of consensus sequence motifs for kinases and phosphorylation-dependent binding domains.
- To analyze signaling systems and kinase specificity, particularly in cancer.
Main Methods:
- Developed an automated pipeline using phylogenetic trees to structure in vivo and in vitro data.
- Derived probabilistic sequence models for linear motifs.
- Compiled data for 179 kinases and 104 binding domains (e.g., SH2, PTB, BRCT, WW, 14-3-3).
Main Results:
- NetPhorest covers 179 kinases and 104 binding domains.
- Discovered that tyrosine kinases mutated in cancer exhibit lower specificity compared to their non-oncogenic counterparts.
- Provides insights into cellular signaling systems and regulatory networks.
Conclusions:
- NetPhorest serves as a valuable community resource for understanding protein phosphorylation.
- The atlas facilitates the matching of phosphorylation sites to kinases and binding domains.
- Findings on kinase specificity have implications for cancer research and drug development.
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