Protein Phosphorylation

Protein phosphorylation is a key mechanism in cellular signaling. This volume presents a state-of-the-art survey of one of the most rapidly developing fields of biochemical research. Written by leading experts, it presents the latest results for some of the most important cellular pathways. Color plates illustrate structural or functional relationships, numerous references provide links to the original literature.

Reversible phosphorylation is one of the major mechanisms of controlling protein activity in all eukaryotic cells. This new edition of Protein Phosphorylation: A Practical Approach provides a comprehensive description of current methods used to study protein phosphorylation and the kinases and phosphatases which catalyse it. It includes protocols for studying phosphorylation in intact cells; analysis of signal transduction pathways, kinase specificity, and kinase interactions; assay and purification of kinases and phosphatases; and identification of substrates. Also covered are cloning and expression protocols and advice on the crystallization of kinases and phosphatases. Protein Phosphorylation: A Practical Approach 2e will therefore be of great value to any researcher investigating aspects of reversible protein phosphrylation.

Protein phosphorylation is one of the most abundant reversible post-translational modifications in eukaryotes. It is involved in virtually all cellular processes by regulating protein function, localization and stability and by mediating protein-protein interactions. Furthermore, aberrant protein phosphorylation is implicated in the onset and progression of human diseases such as cancer and neurodegenerative disorders. In the last years, tens of thousands of in vivo phosphorylation events have been identified by large-scale quantitative phospho-proteomics experiment suggesting that a large fraction of the proteome might be regulated by phosphorylation. This data explosion is increasingly enabling the development of computational approaches, often combined with experimental validation, aiming at prioritizing phosphosites and assessing their functional relevance. Some computational approaches also address the inference of specificity determinants of protein kinases/phosphatases and the identification of phosphoresidue recognition domains. In this context, several challenging issues are still open regarding phosphorylation, including a better understanding of the interplay between phosphorylation and allosteric regulation, agents and mechanisms disrupting or promoting abnormal phosphorylation in diseases, the identification and modulation of novel phosphorylation inhibitors, and so forth. Furthermore, the determinants of kinase and phosphatase recognition and binding specificity are still unknown in several cases, as well as the impact of disease mutations on phosphorylation-mediated signaling. The articles included in this Research Topic illustrate the very diverse aspects of phosphorylation, ranging from structural changes induced by phosphorylation to the peculiarities of phosphosite evolution. Some also provide a glimpse into the huge complexity of phosphorylation networks and pathways in health and disease, and underscore that a deeper knowledge of such processes is essential to identify disease biomarkers, on one hand, and design more effective therapeutic strategies, on the other.

This comprehensive volume focuses on the ways in which synthetic peptides have been exploited in order to expand our understanding of the molecular mechanisms involved in protein phosphorylation. It recognizes that virtually all physiological processes are regulated by protein phosphorylation. It discusses the use of synthetic peptides in studying the catalytic mechanism and regulation of protein kinases. It also includes the chemical synthesis of phosphorylated peptides and preparation of specific antisera. This incredible work has lead to the development of a new generation of peptide inhibitors with potencies of greater magnitude than those previously known. Everyone involved with biochemistry and molecular biology will find this one-of-a-kind resource fascinating and filled with useful information.

The aim of this text is to integrate the processes of protein phosphorylation and dephosphorylation into the complex pathways by which cellular proliferation is driven, bringing together the many different systems of control implicated in the regulation of cell growth. Presents a survey of protein phosphorylation roles in the control of cellular proliferation and differentiation. A large number of protein kinases and phosphatases have been characterised in higher cells, and have been shown to be involved in signal transduction pathways by which growth factors, mitogens, and extracellular agents exert proliferative effects on cells. Important subjects covered include control of gene expression at the transcriptional and translational levels, and roles of the cdk kinases and cyclins in cell cycles regulation. Describes all major families of protein kinases of significance to growth regulation.

A Comprehensive Guide to Crucial Attributes of Therapeutic Proteins in Biological Pharmaceuticals With this book, Dr. Raju offers a valuable resource for professionals involved in research and development of biopharmaceutical and biosimilar drugs. This is a highly relevant work, as medical practitioners have increasingly turned to biopharmaceutical medicines in their search for safe and reliable treatments for complex diseases, while pharmaceutical researchers seek to expand the availability of biopharmaceuticals and create more affordable biosimilar alternatives. Readers receive a thorough overview of the major co-translational modifications (CTMs) and post-translational modifications (PTMs) of therapeutic proteins relevant to the development of biotherapeutics. The majority of chapters detail individual CTMs and PTMs that may affect the physicochemical, biochemical, biological, pharmacokinetic, immunological, toxicological etc. properties of proteins. In addition, readers are guided on the methodology necessary to analyze and characterize these modifications. Thus, readers gain not only an understanding of CTMs/PTMs, but also the ability to design and assess their own structure-function studies for experimental molecules. Specific features and topics include: Discussion of the research behind and expansion of biopharmaceuticals Twenty chapters detailing relevant CTMs and PTMs of proteins, such as glycosylation, oxidation, phosphorylation, methylation, proteolysis, etc. Each chapter offers an introduction and guide to the mechanisms and biological significance of an individual CTM or PTM, including practical guidance for experiment design and analysis An appendix of biologic pharmaceuticals currently on the market, along with an assessment of their PTMs and overall safety and efficacy This volume will prove a key reference on the shelves of industry and academic researchers involved in the study and development of biochemistry, molecular biology, biopharmaceuticals and proteins in medicine, particularly as biopharmaceuticals and biosimilars become ever more prominent tools in the field of healthcare.

This volume explores some of the most exciting recent advances in basic research on protein phosphorylation in health and disease and how this knowledge is leading to advances in the various fields. Contributions from leading authorities Informs and updates on all the latest developments in the field

Proceedings of the NATO Advanced Study Institute on Cellular Regulation by Protein Phosphorylation held at Chateau La Londe les Maures (France), September 5-15, 1990

15 chapters on protein phosphorylation and human health written by expert scientists. Covers most important research hot points, such as Akt, AMPK and mTOR. Bridges the basic protein phosphorylation pathways with human health and diseases. Detailed and comprehensive text with excellent figure illustration.