Phosphoproteomics-based Profiling of Kinase Activities in Cancer Cells

BioRxiv : the Preprint Server for Biology
Jakob WirbelJulio Saez-Rodriguez

Abstract

Cellular signaling, predominantly mediated by phosphorylation through protein kinases, is found to be deregulated in most cancers. Accordingly, protein kinases have been subject to intense investigations in cancer research, to understand their role in oncogenesis and to discover new therapeutic targets. Despite great advances, an understanding of kinase dysfunctioning in cancer is far from complete. A powerful tool to investigate phosphorylation is mass-spectrometry (MS)-based phosphoproteomics, which enables the identification of thousands of phosphorylated peptides in a single experiment. Since every phosphorylation event results from the activity of a protein kinase, high-coverage phosphoproteomics data should indirectly contain comprehensive information about the activity of protein kinases. In this chapter, we discuss the use of computational methods to predict kinase activity scores from MS-based phosphoproteomics data. We start with a short explanation of the fundamental features of the phosphoproteomics data acquisition process from the perspective of the computational analysis. Next, we briefly review the existing databases with experimentally verified kinase-substrate relationships and present a set of bioinformatic t...Continue Reading

Related Concepts

Malignant Neoplasms
Peptides
Phosphorylation
Phosphotransferases
Protein KINASE
Research
Signal Transduction
Mass Spectrometry
Tumor Cells, Malignant
Carcinogenesis

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