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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.
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.
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.
Protein kinase A (PKA) is an enzyme that modulates the function of other proteins and thus is involved in many processes responsible for cellular regulation. This volume follows the discovery of the first human genetic disorder that is caused by mutations of one of the sub-units of the PKA system. It brings together clinical and basic scientists for an examination of the enzyme and its involvement in human disease.
Protein kinases are fascinating enzymes that maintain the proper function of nearly every task performed by the cells of the human body. By extracting a phosphate from the energy molecule ATP and linking it to another protein, protein kinases alter the structure and ultimate function of other proteins. In this way, protein kinases help monitor the extracellular environment and integrate signaling cues that, for the most part, are beneficial for human health and survival. However, protein kinases are often dysregulated and responsible for the initiation and progression of many types of cancers, inflammatory disorders, and other diseases. Thus, decades of research have revealed much about how protein kinases are regulated and approaches to inhibit these enzymes to treat disease. However, nearly 30 years since the identification of the first clinically beneficial small molecule protein kinase inhibitor, there are only a few examples where these drugs provide sustained and durable patient responses. The goal of this book is to provide biomedical scientists, graduate, and professional degree students insight into different approaches using small molecules to block specific protein kinase functions that promote disease.
Basic Neurochemistry, Eighth Edition, is the updated version of the outstanding and comprehensive classic text on neurochemistry. For more than forty years, this text has been the worldwide standard for information on the biochemistry of the nervous system, serving as a resource for postgraduate trainees and teachers in neurology, psychiatry, and basic neuroscience, as well as for medical, graduate, and postgraduate students and instructors in the neurosciences. The text has evolved, as intended, with the science. This new edition continues to cover the basics of neurochemistry as in the earlier editions, along with expanded and additional coverage of new research from intracellular trafficking, stem cells, adult neurogenesis, regeneration, and lipid messengers. It contains expanded coverage of all major neurodegenerative and psychiatric disorders, including the neurochemistry of addiction, pain, and hearing and balance; the neurobiology of learning and memory; sleep; myelin structure, development, and disease; autism; and neuroimmunology. - Completely updated text with new authors and material, and many entirely new chapters - Over 400 fully revised figures in splendid color - 61 chapters covering the range of cellular, molecular and medical neuroscience - Translational science boxes emphasizing the connections between basic and clinical neuroscience - Companion website at http://elsevierdirect.com/companions/9780123749475
Biological processes are driven by complex systems of functionally interacting signaling molecules. Thus, understanding signaling molecules is essential to explain normal or pathological biological phenomena. A large body of clinical and experimental data has been accumulated over these years, albeit in fragmented state. Hence, systems biological approaches concomitant with the understanding of each molecule are ideal to delineate signaling networks/pathways involved in the biologically important processes. The control of these signaling pathways will enrich our healthier life. Currently, there are more than 30,000 genes in human genome. However, not all the proteins encoded by these genes work equally in order to maintain homeostasis. Understanding the important signaling molecules as completely as possible will significantly improve our research-based teaching and scientific capabilities. This encyclopedia presents 350 biologically important signaling molecules and the content is built on the core concepts of their functions along with early findings written by some of the world’s foremost experts. The molecules are described by recognized leaders in each molecule. The interactions of these single molecules in signal transduction networks will also be explored. This encyclopedia marks a new era in overview of current cellular signaling molecules for the specialist and the interested non-specialist alike During past years, there were multiple databases to gather this information briefly and very partially. Amidst the excitement of these findings, one of the great scientific tasks of the coming century is to bring all the useful information into a place. Such an approach is arduous but at the end will infuse the lacunas and considerably be a streamline in the understanding of vibrant signaling networks. Based on this easy-approach, we can build up more complicated biological systems.
This volume details the current understanding of roles and regulation on histidine phosphorylation, describing methods for the characterization of protein phosphorylation on histidine. Chapters guide readers through in vitro systems, cell-based systems, comprehensive background review articles on histidine kinases and phosphatases. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and cutting-edge, Histidine Phosphorylation: Methods and Protocols aims to ensure successful results in the further study of this rapidly growing field.
The present volume of the Handbook of Experimental Pharmacology gives a representative survey of the current status of the structure, function, regulation and molecular pharmacology of Neurotransmitter Transporters and aims at providing an overview of insights that were generated in the past 5 years. If the volume serves as both, a useful compendium of current concepts and an inspiring starting point, it will have fulfilled its mission and will be a source for students interested in this emerging field as well as for experienced scientists looking for an update. This volume is the brainchild of the editor-in-chief of the HEP series, Klaus Starke, awe-inspiring to all pharmacologists of younger generations.