Cell signalling analyses in the functional genomics era

The advancements in proteomics over the past decade have brought tremendous increases in sensitivity of mass spectrometry (MS) analyses and new technologies such as methods for quantitative MS and phosphoproteomics. The development of antibodies targeting a large fraction of the human proteome as well as specific antibodies that detect phosphorylations and other post-translational modifications now allows detection of a great variety of signalling marks. Combined with medium and high throughput methods for detecting many parallel signalling events such as phospho-flow cytometry analyses and MS-based analyses to identify signalling complexes, the available tools now allows analysis of whole signalling networks facilitating systems level understanding of cellular signalling. The even more recent advances in chemical biology and chemical proteomics are further enhancing the development in this area by providing a cache of small molecule compounds allowing perturbations of signal pathways further advancing our global understanding of the signal transduction dynamics at the single cell level as well as in cellular system, tissue and whole organs. This review highlights the recent advances of quantitative MS, phosphoflow cytometry and chemical biology with focus on the dynamic spatiotemporal phosphorylation events, and examples of their application.