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This new volume of Methods in Enzymology continues the legacy of this premier serial with quality chapters authored by leaders in the field. This is the second of three volumes on hydrogen peroxide and cell signaling, and includes chapters on such topics as the cellular steady-state of H2O2, evaluating peroxiredoxin sensitivity towards inactivation by peroxide substrates, and peroxiredoxins as preferential targets in H2O2-induced signaling.
Driving further the research on mammalian alkaline phosphatase structure and function, Phosphatase Modulators collects expert contributions into one “how to” manual for basic scientists interested in initiating a drug discovery effort. While this book contains the traditional method chapters and some typical reviews on the structure and known functions of phosphatases, other contributions are meant to discuss approaches and alternatives useful in making “go/no-go” decisions in high throughput screening (HTS) and lead optimization campaigns. Many chapters focus on tissue-nonspecific alkaline phosphatase (TNAP) as well as protein phosphatases. Written for the highly successful Methods in Molecular Biology series, chapters in this volume include the kind of detail and key implementation advice that promotes reproducible results. Step-by-step and practical, Phosphatase Modulators offers a path to understanding many of the facets and complexities associated with undertaking a drug discovery effort and will serve as a roadmap to initiating those efforts.
A comprehensive review of stress signaling in plants using genomics and functional genomic approaches Improving agricultural production and meeting the needs of a rapidly growing global population requires crop systems capable of overcoming environmental stresses. Understanding the role of different signaling components in plant stress regulation is vital to developing crops which can withstand abiotic and biotic stresses without loss of crop yield and productivity. Emphasizing genomics and functional genomic approaches, Protein Kinases and Stress Signaling in Plants is a comprehensive review of cutting-edge research on stress perception, signal transduction, and stress response generation. Detailed chapters cover a broad range of topics central to improving agricultural production developing crop systems capable of overcoming environmental stresses to meet the needs of a rapidly growing global population. This book describes the field of protein kinases and stress signaling with a special emphasis on functional genomics. It presents a highly valuable contribution in the field of stress perception, signal transduction and generation of responses against one or multiple stress signals. This timely resource: Summarizes the role of various kinases involved in stress management Enumerates the role of TOR, GSK3-like kinase, SnRK kinases in different physiological conditions Examines mitogen-activated protein kinases (MAPKs) in different stresses Describes the different aspects of calcium signaling under different stress conditions Examines photo-activated kinases (PAPKs) in varying light conditions Briefs the presence of tyrosine kinases in plants Highlights the cellular functions of receptor ]like protein kinases (RLKs) Possible implication of these kinases in developing stress tolerant crops Protein Kinases and Stress Signaling in Plants: Functional Genomic Perspective is an essential resource for researchers and students in the fields of plant molecular biology and signal transduction, plant responses to stress, plant cell signaling, plant protein kinases, plant biotechnology, transgenic plants and stress biology.
Thoroughly revised and updated, this Third Edition encompasses the most recent advances in molecular and cellular research and describes the newest therapeutic modalities for type 1 and type 2 diabetes mellitus. Chapters by leading experts integrate the latest basic science and clinical research on diabetes mellitus and its complications. The text is divided into ten major sections, including extensive sections on therapeutics, diabetes during pregnancy, and complications. New chapters cover stem cell therapy for type 1 diabetes; genetics and treatment of obesity; new therapies to promote insulin action; vasculopathy; islet cell protocols; triglycerides in muscle; hypoglycemia in the adult; and the Diabetes Prevention Program.
Handbook of Cell Signaling, Three-Volume Set, 2e, is a comprehensive work covering all aspects of intracellular signal processing, including extra/intracellular membrane receptors, signal transduction, gene expression/translation, and cellular/organotypic signal responses. The second edition is an up-to-date, expanded reference with each section edited by a recognized expert in the field. Tabular and well illustrated, the Handbook will serve as an in-depth reference for this complex and evolving field. Handbook of Cell Signaling, 2/e will appeal to a broad, cross-disciplinary audience interested in the structure, biochemistry, molecular biology and pathology of cellular effectors. - Contains over 350 chapters of comprehensive coverage on cell signaling - Includes discussion on topics from ligand/receptor interactions to organ/organism responses - Provides user-friendly, well-illustrated, reputable content by experts in the field
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.
Dual specificity phosphatases (DUSPs) constitute a heterogeneous group of protein tyrosine phosphatases with the ability to dephosphorylate Ser/Thr and Tyr residues from proteins, as well as from other non-proteinaceous substrates including signaling lipids. DUSPs include, among others, MAP kinase (MAPK) phosphatases (MKPs) and small-size atypical DUSPs. MKPs are enzymes specialized in regulating the activity and subcellular location of MAPKs, whereas the function of small-size atypical DUSPs seems to be more diverse. DUSPs have emerged as key players in the regulation of cell growth, differentiation, stress response, and apoptosis. DUSPs regulate essential physiological processes, including immunity, neurobiology and metabolic homeostasis, and have been implicated in tumorigenesis, pathological inflammation and metabolic disorders. Accordingly, alterations in the expression or function of MKPs and small-size atypical DUSPs have consequences essential to human disease, making these enzymes potential biological markers and therapeutic targets. This Special Issue covers recent advances in the molecular mechanisms and biological functions of MKPs and small-size atypical DUSPs, and their relevance in human disease.
Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a highly prevalent hereditary renal disorder in which fluid-filled cysts are appeared in both kidneys. Main causative genes of ADPKD are PKD1 and PKD2, encoding for polycystin-1 (PC1) and polycystin-2 (PC2) respectively. Those proteins are localized on primary cilia and function as mechanosensor in response to the fluid flow, translating mechanistic stimuli into calcium signaling. With mutations either of PKD1 or PKD2, hyper-activated renal tubular epithelial cell proliferation is observed, followed by disrupted calcium homeostasis and aberrant intracellular cyclic AMP (cAMP) accumulation. Increased cell proliferation with fluid secretion leads to the development of thousands of epithelial-lined, fluid-filled cysts in kidneys. It is also accompanied by interstitial inflammation, fibrosis, and finally reaching end-stage renal disease (ESRD). In human ADPKD, the age at which renal failure typically occurs is later in life, however no specific targeted medications are available to cure ADPKD. Recently, potential therapeutic targets or surrogate diagnostic biomarkers for ADPKD are proposed with the advances in the understanding of ADPKD pathogenesis, and some of them were attempted for clinical trials. Herein, we will summarize genetic and epi-genetic molecular mechanisms in ADPKD progression, and overview the currently available biomarkers or potential therapeutic reagents suggested.
PROVIDES STRATEGIES AND CONCEPTS FOR UNDERSTANDING CHEMICAL PROTEOMICS, AND ANALYZING PROTEIN FUNCTIONS, MODIFICATIONS, AND INTERACTIONS—EMPHASIZING MASS SPECTROMETRY THROUGHOUT Covering mass spectrometry for chemical proteomics, this book helps readers understand analytical strategies behind protein functions, their modifications and interactions, and applications in drug discovery. It provides a basic overview and presents concepts in chemical proteomics through three angles: Strategies, Technical Advances, and Applications. Chapters cover those many technical advances and applications in drug discovery, from target identification to validation and potential treatments. The first section of Mass Spectrometry-Based Chemical Proteomics starts by reviewing basic methods and recent advances in mass spectrometry for proteomics, including shotgun proteomics, quantitative proteomics, and data analyses. The next section covers a variety of techniques and strategies coupling chemical probes to MS-based proteomics to provide functional insights into the proteome. In the last section, it focuses on using chemical strategies to study protein post-translational modifications and high-order structures. Summarizes chemical proteomics, up-to-date concepts, analysis, and target validation Covers fundamentals and strategies, including the profiling of enzyme activities and protein-drug interactions Explains technical advances in the field and describes on shotgun proteomics, quantitative proteomics, and corresponding methods of software and database usage for proteomics Includes a wide variety of applications in drug discovery, from kinase inhibitors and intracellular drug targets to the chemoproteomics analysis of natural products Addresses an important tool in small molecule drug discovery, appealing to both academia and the pharmaceutical industry Mass Spectrometry-Based Chemical Proteomics is an excellent source of information for readers in both academia and industry in a variety of fields, including pharmaceutical sciences, drug discovery, molecular biology, bioinformatics, and analytical sciences.