Technical Phosphoproteomic and Bioinformatic Tools useful in Cancer Research

Reversible protein phosphorylation is one of the most important forms of cellular regulation. Thus, phosphoproteomic analysis of protein phosphorylation in cells is a powerful tool to evaluate cell functional status. The importance of protein kinase-regulated signal transduction pathways in human cancer has led to the development of drugs that inhibit protein kinases at the apex or intermediary levels of these pathways. Phosphoproteomic analysis of these signalling pathways will provide important insights for operation and connectivity of these pathways to facilitate identification of the best targets for cancer therapies. Enrichment of phosphorylated proteins or peptides from tissue or bodily fluid samples is required. The application of technologies such as phosphoenrichments, mass spectrometry (MS) coupled to bioinformatics tools is crucial for the identification and quantification of protein phosphorylation sites for advancing in such relevant clinical research. A combination of different phosphopeptide enrichments, quantitative techniques and bioinformatic tools is necessary to achieve good phospho-regulation data and good structural analysis of protein studies. The current and most useful proteomics and bioinformatics techniques will be explained with research examples. Our aim in this article is to be helpful for cancer research via detailing proteomics and bioinformatic tools.
This study was supported by: the Spanish Ministerio de Ciencia e Innovación through grants SAF2007-61926 (to PGP) and the European Commission through grant FP7 HEALTH-F3-2009-223431 (to PGP). Biomol-Informatics was financed by the European Social Fund. Support from the "Fundación Ramón Areces" is acknowledged. We also thank the Centro de Computación Científica-UAM for computational support. Special thanks Prof. Ernest Feytmans (Honorary Director at Swiss Institute of Bioinformatics -Location Geneva Area, Switzerland) and Prof. Shabaz Mohammed (Theme Leader at the Netherlands Proteomics Centre, Lecturer Utrecht University) who contributed to the publication of this article.