Targeted MS of Phopho-signaling Pathways

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Targeted MS of Phopho-signaling Pathways 2016-11-10T20:28:45+00:00

Notable peer-reviewed articles—MS-based phosphoproteomics to detect phosphorylation for study of phospho- and cellular signaling pathways and networks.

 

Articles of note

Cell signalling analysesCell 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. Read more ›

Preliminary simplified model of the broad categories of regulatory molecules controlling pluripotency and differentiation of stem cells, which is consistent with general cell biology.Phosphoproteomic analysis: an emerging role in deciphering cellular signaling in human embryonic stem cells and their differentiated derivatives

Cellular signaling is largely controlled by protein phosphorylation. This post-translational modification (PTM) has been extensively analyzed when examining one or a few protein phosphorylation events that effect cell signaling. However, protein kinase-driven signaling networks, comprising total (phospho)proteomes, largely control cell fate. Therefore, large-scale analysis of differentially regulated protein phosphorylation is central to elucidating complex cellular events, including maintenance of pluripotency and differentiation of embryonic stem cells (ESCs). The current technology of choice for total phosphoproteome and combined total proteome plus total phosphoproteome (termed (phospho)proteome) analyses is multidimensional liquid chromatography-(MDLC) tandem mass spectrometry (MS/MS). Read more ›

Modeling signaling networks using high-throughput phospho-proteomics

Cellular communication and information processing is performed by complex, dynamic, and context specific signaling networks. Mathematical modeling is a very useful tool to make sense of this complexity. Building a model relies on two main ingredients: data and an adequate model formalism. In the case of signaling networks, we build mainly upon data at the proteome level, in particular about the phosphorylation of proteins. In this chapter we review recent developments in both data acquisition and computational analysis. We describe two approaches, antibody based technologies and mass spectrometry (MS), along with their main features and limitations. Read more ›

Phosphoproteomic profiling and network-based discovery of phospho-signatures.

Phosphoproteomic profiling and network-based discovery of phospho-signatures.

Phosphoproteomics-based network medicine (free full text)

One of the major tasks of phosphoproteomics is providing potential biomarkers for either diagnosis or drug targets in medical applications. Because most complex diseases are due to the actions of multiple genes/proteins, the identification of complex phospho-signatures containing multiple phosphorylation events within phosphoproteomics-based networks generates more efficient and robust biomarkers than a single, differentially phosphorylated substrate or site. Here, we briefly summarize the current efforts and progress in this newly emerging field of phosphoproteomics-based network medicine by reviewing the computational (re)construction of phosphorylation-mediated signaling networks from unannotated phosphoproteomic data, the discovery of robust network phospho-signatures and the application of these signatures for classifying cancers and predicting drug responses. Read more ›

Analysing signalling networks by mass spectrometry

Sequence analysis of the human genome and the association of genetic aberrations with diseases have provided a rough framework whereby the impact of individual genotypes can be assessed. To fully understand the effect of individual and co-occurring genetic aberrations, as well as their individual and collected contribution to the development of diseases, it is critical to analyse the matching proteome and to determine how the organisation, expression level and function of protein networks are affected.  Read more ›

Platforms for enrichmentPlatforms for enrichment of phosphorylated proteins and peptides in proteomics

Protein phosphorylation is a complex and highly dynamic process involved in numerous biological events. Abnormal phosphorylation is one of the underlying mechanisms for the development of cancer and metabolic disorders. The identification and absolute quantification of specific phospho-signatures can help elucidate protein functions in signaling pathways and facilitate the development of new and personalized diagnostic and therapeutic tools. This review presents a variety of strategies currently utilized for the enrichment of phosphorylated proteins and peptides before mass spectrometry analysis during proteomic studies. Read more ›