This book provides an essential overview of the role of phosphoinositide-3-phosphate kinase (PI3K) isoforms in modulating the function of immune system cells and their involvement in disease. PI3K is a family of kinases involved in basic cellular processes such as proliferation, migration and cell death. Recent work has highlighted the multiple roles of PI3K classes and subunits and their involvement in the immune response to the body's own and foreign antigens and diseases such as cancer and autoimmunity. This book offers a detailed introduction to the biology of the three PI3K classes, followed by an extensive discussion of the diverse roles of AKT and PI3K isoforms in immune cells. Based on this knowledge, it subsequently explains in more detail how specific isoforms are connected to immune-mediated diseases. The book concludes by highlighting the latest advances in the production of isoform-specific inhibitors and their use in various human diseases. This book is intended as a reference guide for students and researchers interested in the multifaceted aspects of PI3K biology.

The PI3Ks control many key functions in immune cells. PI3Ks phosphorylate PtdIns(4,5)P2 to yield PtdIns(3,4,5)P3. Initially, PI3K inhibitors such as Wortmannin, LY294002 and Rapamycin were used to establish a central role for Pi3K pathway in immune cells. Considerable progress in understanding the role of this pathway in cells of the immune system has been made in recent years, starting with analysis of various PI3K and Pten knockout mice and subsequently mTOR and Foxo knockout mice. Together, these experiments have revealed how PI3Ks control B cell and T cell development, T helper cell differentiation, regulatory T cell development and function, B cell and T cell trafficking, immunoglobulin class switching and much, much more. The PI3Kd inhibitor idelalisib has recently been approved for the treatment of B cell lymphoma. Clinical trials of other PI3K inhibitors in autoimmune and inflammatory diseases are also in progress. This is an opportune time to consider a Research Topic considering when what we have learned about the PI3K signalling module in lymphocyte biology and how this is making an impact on clinical immunology and haematology.

Structure and Intrinsic Disorder in Enzymology offers a direct, yet comprehensive presentation of the fundamental concepts, characteristics and functions of intrinsically disordered enzymes, along with valuable notes and technical insights powering new research in this emerging field. Here, more than twenty international experts examine protein flexibility and cryo-enzymology, hierarchies of intrinsic disorder, methods for measurement of disorder in proteins, bioinformatics tools for predictions of structure, disorder and function, protein promiscuity, protein moonlighting, globular enzymes, intrinsic disorder and allosteric regulation, protein crowding, intrinsic disorder in post-translational, and much more. Chapters also review methods for study, as well as evolving technology to support new research across academic, industrial and pharmaceutical labs. Unifies the roles of intrinsic disorder and structure in the functioning of enzymes and proteins Examines a range of enzyme and protein characteristics, their relationship to intrinsic disorder, and methods for study Features chapter contributions from international leaders in the field

This book aims to bridge the gap in understanding how protein-tyrosine phosphatases (PTPs), which carry out the reverse reaction of tyrosine phosphorylation, feature in cancer cell biology. The expertly authored chapters will first review the general features of the PTP superfamily, including their overall structure and enzymological properties; use selected examples of individual PTP superfamily members, to illustrate emerging data on the role of PTPs in cancer; and will review the current status of PTP-based drug development efforts. Protein Tyrosine Phosphatases in Cancer,from renowned researchers Benjamin Neel and Nicholas Tonks, is invaluable reading for researchers in oncology, stem cell signaling,and biochemistry.

This book series consists of 3 volumes covering the basic science (Volume 1), clinical science (Volume 2) and the technology and methodology (Volume 3) of autophagy. Volume 1 focuses on the biology of autophagy, including the signaling pathways, regulating processes and biological functions. Autophagy is a fundamental physiological process in eukaryotic cells. It not only regulates normal cellular homeostasis, and organ development and function, but also plays an important role in the pathogenesis of a wide range of human diseases. Thanks to the rapid development of molecular biology and omic technologies, research on autophagy has boomed in recent decades, and more and more cellular and animal models and state-of the-art technologies are being used to shed light on the complexity of signaling networks involved in the autophagic process. Further, its involvement in biological functions and the pathogenesis of various diseases has attracted increased attention around the globe. Presenting cutting-edge knowledge, this book series is a useful reference resource for researchers and clinicians who are working on or interested in autophagy.

This report considers the biological and behavioral mechanisms that may underlie the pathogenicity of tobacco smoke. Many Surgeon General's reports have considered research findings on mechanisms in assessing the biological plausibility of associations observed in epidemiologic studies. Mechanisms of disease are important because they may provide plausibility, which is one of the guideline criteria for assessing evidence on causation. This report specifically reviews the evidence on the potential mechanisms by which smoking causes diseases and considers whether a mechanism is likely to be operative in the production of human disease by tobacco smoke. This evidence is relevant to understanding how smoking causes disease, to identifying those who may be particularly susceptible, and to assessing the potential risks of tobacco products.