Signal Transduction

Michael F. Moran Cells respond to various signals that govern their basic and specific cellular processes. A thorough understanding of the molecular mechanisms involved in cellular signaling is essential as aberrant signaling pathways are implicated in a number of diseases. Studying signaling in disease states forms the basis to developing novel therapeutic strategies. To understand signaling mechanisms in detail, systematic approaches have been developed to comprehensively characterize post-translational modifications (PTMs) such as phosphorylation under various conditions. Recent advances in mass spectrometry-based and array-based approaches have made it possible for the global characterization of signaling pathways. This Special Issue of PROTEOMICS brings together a collection of proteomics studies on signaling carried out by experts in the field of proteomics. This issue comprises a total of 36 contributions from various experts in the field of proteomics and signaling research. The compiled articles cover various topics relevant to the current progress in PTM analysis and delineating signaling mechanisms in health and disease. The first part of this special issue consists of 10 review articles covering diverse areas of research on cell signaling and disease. To date, several approaches have been developed to characterize signaling pathways. In the past decade, mass spectrometry has been used extensively in biological research and has aided effectively in addressing important biological questions. Three groups independently review the current progress in the understanding signaling networks using proteomics-based approaches. The review by Li et al., focuses on recent advances in affinity purification-MS to study protein-protein interactions. Vivelo et al., review in detail the strategies employed for efficient enrichment of ADP-ribosylated proteins and their associated proteins by mass spectrometry, their advantages, limitations and pitfalls. Gahoi et al., review the advantages, disadvantages and applications of various array-based techniques to study the interactions and modifications of biomolecules, their association with signaling pathways and their correlation with disease pathobiology. SRC, a non-receptor tyrosine kinase is a critical regulator of signal transduction plays an essential role in controlling cell growth and migration. Deregulation in SRC signaling is frequently observed in human cancer and is thought to play important roles during tumourigenesis. Sirvent et al., review the current phosphoproteomic strategies that have provided new insights into SRC signaling in normal and cancer cells. Batkulwar and colleagues review the signaling pathways activated by receptor for advanced glycation end products (RAGE) activated kinases. The article also provides insight on the plausible role of RAGE activated phosphoproteome in several diseases. Two reviews in the issue focus on the emerging role of extracellular vesicles as mediators of signaling by means of protein and RNA transfer through paracrine and autocrine manner. The article by Gangoda et al., provides a comprehensive review on extracellular vesicles (EVs) as mediators of signal transduction in cancer as well as neurodegenerative diseases. The authors also emphasize the need for additional studies to obtain a clear understanding of the complex role that extracellular vesicles play in physiological and pathological conditions. Havrylov et al., review the current progresses and challenges in proteomic strategies employed to characterize proteins and PPIs in these invasive cell structures. The other reviews focus on the current progress in elucidation of signaling mechanisms. Yuan and colleagues review the recent advances in the proteomics approaches developed to understand the altered functions of redox sensors and its role in cancer. Angiogenesis is a vital physiological process and plays an important role in numerous pathological conditions. Rahimi and Costello review the significance of post-translational modifications on vascular endothelial growth factor receptor-2 (VEGFR-2) in signaling, angiogenesis and potential therapeutic