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Updated: Apr 19, 2026

Identification of Kinase-substrate Pairs Using High Throughput Screening
Published on: August 29, 2015
Computational methods and opportunities for phosphorylation network medicine
Yian Ann Chen1, Steven A Eschrich1
1Department of Biostatistics and Bioinformatics, Moffitt Cancer Center, 12902 Magnolia Drive Tampa, FL 33612, USA.
Abstract:
Protein phosphorylation, one of the most ubiquitous post-translational modifications (PTM) of proteins, is known to play an essential role in cell signaling and regulation. With the increasing understanding of the complexity and redundancy of cell signaling, there is a growing recognition that targeting the entire network or system could be a necessary and advantageous strategy for treating cancer. Protein kinases, the proteins that add a phosphate group to the substrate proteins during phosphorylation events, have become one of the largest groups of 'druggable' targets in cancer therapeutics in recent years. Kinase inhibitors are being regularly used in clinics for cancer treatment. This therapeutic paradigm shift in cancer research is partly due to the generation and availability of high-dimensional proteomics data. Generation of this data, in turn, is enabled by increased use of mass-spectrometry (MS)-based or other high-throughput proteomics platforms as well as companion public databases and computational tools. This review briefly summarizes the current state and progress on phosphoproteomics identification, quantification, and platform related characteristics. We review existing database resources, computational tools, methods for phosphorylation network inference, and ultimately demonstrate the connection to therapeutics. Finally, many research opportunities exist for bioinformaticians or biostatisticians based on developments and limitations of the current and emerging technologies.
Insights
Protein phosphorylation is crucial for cell signaling and cancer treatment. Advances in phosphoproteomics and kinase inhibitors offer new therapeutic strategies by targeting complex cellular networks.
Area of Science:
- Biochemistry
- Cell Biology
- Bioinformatics
Background:
- Protein phosphorylation is a key post-translational modification regulating cell signaling.
- Cancer research increasingly targets complex signaling networks due to their complexity and redundancy.
- Protein kinases are major drug targets in cancer therapy, with inhibitors widely used clinically.
Purpose of the Study:
- To review the current state of phosphoproteomics for identifying and quantifying protein phosphorylation.
- To discuss platform characteristics, database resources, and computational tools in phosphoproteomics.
- To highlight the connection between phosphoproteomics advancements and cancer therapeutics.
Main Methods:
- Review of high-throughput proteomics platforms, particularly mass-spectrometry (MS)-based methods.
- Analysis of existing public databases and computational tools for phosphoproteomics data.
- Examination of methods for inferring phosphorylation networks.
Main Results:
- Phosphoproteomics, driven by MS and high-throughput platforms, provides high-dimensional data essential for cancer research.
- Numerous database resources and computational tools are available to support phosphoproteomics analysis.
- Inference of phosphorylation networks is advancing, linking molecular insights to therapeutic strategies.
Conclusions:
- Phosphoproteomics advancements are critical for understanding cell signaling and developing targeted cancer therapies.
- The integration of phosphoproteomics data, computational tools, and network inference offers significant opportunities for therapeutic development.
- Future research in bioinformatics and biostatistics is essential to address limitations and leverage emerging technologies in phosphoproteomics.
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