Download or read book Mechanisms of G Protein Regulation by RGS Proteins and Small Molecule Inhibitors written by Stanley Michinobu Kanai and published by . This book was released on 2017 with total page 114 pages. Available in PDF, EPUB and Kindle. Book excerpt: G protein coupled receptors transduce diverse extracellular signals like hormones, neurotransmitters, and photons to specific cellular responses through heterotrimeric G proteins. G proteins activate numerous effectors and signal transduction pathways, and therefore the regulation of G proteins is crucial for faithful propagation of specific cellular and physiological responses. A better understanding of the mechanisms that regulate G proteins should provide new insight into signaling pathways that govern healthy and disease states, and also provide opportunities for discovery of novel therapeutic targets.Regulator of G protein signaling (RGS) proteins are crucial regulators of G proteins, for they control amplitude and duration of G protein signaling responses. RGS2 is particularly important because it is associated with many physiological and disease processes. A key concept that has emerged is that physiological and disease processes are extremely sensitive to even modest changes in RGS2 expression levels. The goals of this dissertation were to investigate the mechanism that controls RGS2 levels and to determine how dynamic RGS2 levels affect GPCR signaling. The particular focus was on the ubiquitin proteasome pathway (UPP), which is one of the key mechanisms that control RGS2 expression levels. Rather than looking for components of the UPP that recognize and degrade RGS2, a comprehensive analysis was performed on the RGS2 N-terminal domain to identify signals required for degradation. This analysis revealed a novel bipartite hydrophobic motif that is required for degradation. Intriguingly, deletion of these hydrophobic motifs did not abrogate binding with E3 ligases associated with RGS2 degradation, suggesting additional mechanisms are involved. The effect of UPP mediated degradation of RGS2 on regulation of GPCR signaling was also explored. Using a cell based, kinetically resolved, GPCR reporter assay, it was demonstrated that proteasome degradation of RGS2 dynamically regulates GPCR signaling, influencing both agonist efficacy and the rate of receptor resensitization.G protein signaling pathways also can be modulated by small molecule inhibitors. YM-254890 and FR900359 are a class of small molecule inhibitors for G proteins that are selective and cell permeable. They are promising research tools and leads for therapeutic agents, but the exact molecular mechanism of action of these inhibitors is not known. The second part of the dissertation describes early stages of a study that aims to elucidate the mechanism of action of YM and FR. Preliminary results that support an allosteric model of inhibition are reported, followed by a discussion of future work that will further test this model.
Download or read book Understanding Specificity of Small Molecule Inhibitors of Regulators of G protein Signaling rgs Proteins written by Vincent Shaw and published by . This book was released on 2019 with total page 201 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Mechanism and Specificity of G Protein Regulation by RGS Proteins written by Keng-Li Lan and published by . This book was released on 1999 with total page 442 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book G Protein Signaling written by Alan V. Smrcka and published by Humana Press. This book was released on 2003-09-15 with total page 250 pages. Available in PDF, EPUB and Kindle. Book excerpt: A collection of cutting-edge methods for investigating G protein signaling from a variety of perspectives ranging from in vitro biochemistry to whole animal studies. Among the readily reproducible techniques presented are those for the purification of G proteins and effectors enzymes, assays of these purified G proteins and effector enzymes, and for the study of G proteins interactions with effectors in intact cells. Additional methods are provided for assaying G protein coupled receptor structure, function, and localization; for studying the physiological roles for endogenous G proteins; and for examining lipid and phosphate modifications of RGS proteins.
Download or read book Molecular Biology of The Cell written by Bruce Alberts and published by . This book was released on 2002 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Molecular Mechanisms Regulating G Protein Signaling in Brain and Heart written by Ekaterina N. Posokhova and published by . This book was released on 2012 with total page 100 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Encyclopedia of Signaling Molecules written by Sangdun Choi and published by Springer. This book was released on 2017-12-15 with total page 6330 pages. Available in PDF, EPUB and Kindle. Book excerpt: The second edition of this encyclopedia presents over 400 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. 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.
Download or read book Regulation of G Protein Signaling by GoLoco Motif Containing Proteins written by Peishen Zhao and published by . This book was released on 2011 with total page 492 pages. Available in PDF, EPUB and Kindle. Book excerpt: Signal transduction via heterotrimeric G proteins in response to transmembrane G protein-coupled receptors plays a central aspect in how cells integrate extracellular stimuli and produce biological responses. In addition to receptor-mediated activation of heterotrimeric G proteins, during the last few decades, accessory proteins have been found to regulate G protein activity via different mechanisms. Several proteins have been identified that contain multiple G protein regulatory domains. Using various molecular and biochemical approaches, we have characterized the effects of two such proteins, G18 and RGS14, on G protein activity. Both proteins contain a second G protein binding domain in addition to the GoLoco domain, which primarily acts as a guanine nucleotide dissociation inhibitor (GDI) on Gi/o proteins. Our results identified that the N-terminal region of G18 is a novel G protein-interacting domain, which may have distinct regulatory effects within the Gi/o subfamily and could potentially play a role in differentiating signals between these related G proteins. In addition, we characterized the tissue and cellular distribution of G18. We found that G18 is expressed in primary isolated rat aortic smooth muscle cells and endothelial cells. A protein-protein interaction assay indicated that G18 is able to directly interact with RGS5, an RGS protein that is also highly expressed in vascular tissue. This interaction results in an increase in RGS5 GTPase accelerating protein (GAP) activity with little or no effect on G18 activity. In Chapter 4 of the thesis, we identified a novel GAP enhancing domain located at the Rasbinding (RB) region of RGS14. This enhancement may be due to the intramolecular interaction between the RB domain and the RGS domain. Furthermore, this interaction may also result in an inhibitory effect on the GDI activity of the RGS14 GoLoco motif. Overall, my work suggests that GoLoco motif containing proteins G18 and RGS14 are organizers of G protein signaling that also modulate RGS protein function.
Download or read book Neuromorphic Olfaction written by Krishna C. Persaud and published by CRC Press. This book was released on 2016-04-19 with total page 237 pages. Available in PDF, EPUB and Kindle. Book excerpt: Many advances have been made in the last decade in the understanding of the computational principles underlying olfactory system functioning. Neuromorphic Olfaction is a collaboration among European researchers who, through NEUROCHEM (Fp7-Grant Agreement Number 216916)-a challenging and innovative European-funded project-introduce novel computing p
Download or read book G Protein Pathways Part A Receptors written by and published by Academic Press. This book was released on 2001-10-09 with total page 719 pages. Available in PDF, EPUB and Kindle. Book excerpt: G Protein Pathways is the first of three volumes examining the nature of heterotrimeric G proteins. The text takes an integrated approach to studying common experimental questions at many different levels related to G proteins. Methods related to G proteins using molecular modeling, systems biology, protein engineering, protein biochemistry, cell biology, and physiology are all accessible in the same volume. The critically acclaimed laboratory standard for more than forty years, Methods in Enzymology is one of the most highly respected publications in the field of biochemistry. Since 1955, each volume has been eagerly awaited, frequently consulted, and praised by researchers and reviewers alike. Now with more than 300 volumes (all of them still in print), the series contains much material still relevant today truly an essential publication for researchers in all fields of life sciences.
Download or read book Principles of Endocrinology and Hormone Action written by Antonino Belfiore and published by Springer. This book was released on 2018-02-08 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume provides comprehensive coverage of the current knowledge of the physiology of the endocrine system and hormone synthesis and release, transport, and action at the molecular and cellular levels. It presents essential as well as in-depth information of value to both medical students and specialists in Endocrinology, Gynecology, Pediatrics, and Internal Medicine. Although it is well established that the endocrine system regulates essential functions involved in growth, reproduction, and homeostasis, it is increasingly being recognized that this complex regulatory system comprises not only hormones secreted by the classic endocrine glands but also hormones and regulatory factors produced by many organs, and involves extensive crosstalk with the neural and immune system. At the same time, our knowledge of the molecular basis of hormone action has greatly improved. Understanding this complexity of endocrine physiology is crucial to prevent endocrine disorders, to improve the sensitivity of our diagnostic tools, and to provide the rationale for pharmacological, immunological, or genetic interventions. It is such understanding that this book is designed to foster.
Download or read book RGS Protein Physiology and Pathophysiology written by and published by Academic Press. This book was released on 2015-06-23 with total page 243 pages. Available in PDF, EPUB and Kindle. Book excerpt: RGS Protein Physiology and Pathophysiology describes the current, state-of-the-art research occurring in the laboratories of leaders in the RGS protein field that utilize genetic mouse models to interrogate the function of RGS proteins in vivo. Each chapter describes the elucidated role of a specific RGS protein or family of RGS proteins in normal physiology and/or disease with particular emphasis on how these discoveries inform healthcare and drug discovery. The work is a timely reference as drugs targeting G protein coupled receptors represent 40% of currently marketed therapeutics. Brings together information on the current state of the RGS protein field Contains comprehensive descriptions of the known pathophysiological and physiological functions of RGS proteins, the first such undertaking Gives particular emphasis to the ways these discoveries inform healthcare and drug discovery
Download or read book Fungal Biotechnology and Bioengineering written by Abd El-Latif Hesham and published by Springer. This book was released on 2020-08-08 with total page 482 pages. Available in PDF, EPUB and Kindle. Book excerpt: Fungi are eukaryotic microorganisms that include both unicellular and multicellular species. They have a worldwide distribution and a wide range of applications in diverse sectors, from environmental, food and medicine to biotechnological innovations. Fungal biochemical genetics involves the study of the relationships between genome, proteome and metabolome, and the underlying molecular processes in both native and bioengineered fungi. This book provides a valuable resource on the challenges and potential of fungal biotechnology and related bioengineering and functional diversity for various industrial applications in the food, environmental, bioenergy and biorefining, and the biopharma sectors. In comparison to previous and related publications in the area of applied myco-biotech-engineering, this book bridges a knowledge gap in the areas related to prospects and investment as well as intellectual and technical issues. This book also provides information on recent commercial and economic interests in the area by juxtaposing the developments achieved in recent worldwide research and its many challenges.
Download or read book Colonic Motility written by Sushil K. Sarna and published by Biota Publishing. This book was released on 2010-11-01 with total page 159 pages. Available in PDF, EPUB and Kindle. Book excerpt: Three distinct types of contractions perform colonic motility functions. Rhythmic phasic contractions (RPCs) cause slow net distal propulsion with extensive mixing/turning over. Infrequently occurring giant migrating contractions (GMCs) produce mass movements. Tonic contractions aid RPCs in their motor function. The spatiotemporal patterns of these contractions differ markedly. The amplitude and distance of propagation of a GMC are several-fold larger than those of an RPC. The enteric neurons and smooth muscle cells are the core regulators of all three types of contractions. The regulation of contractions by these mechanisms is modifiable by extrinsic factors: CNS, autonomic neurons, hormones, inflammatory mediators, and stress mediators. Only the GMCs produce descending inhibition, which accommodates the large bolus being propelled without increasing muscle tone. The strong compression of the colon wall generates afferent signals that are below nociceptive threshold in healthy subjects. However, these signals become nociceptive; if the amplitudes of GMCs increase, afferent nerves become hypersensitive, or descending inhibition is impaired. The GMCs also provide the force for rapid propulsion of feces and descending inhibition to relax the internal anal sphincter during defecation. The dysregulation of GMCs is a major factor in colonic motility disorders: irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), and diverticular disease (DD). Frequent mass movements by GMCs cause diarrhea in diarrhea predominant IBS, IBD, and DD, while a decrease in the frequency of GMCs causes constipation. The GMCs generate the afferent signals for intermittent short-lived episodes of abdominal cramping in these disorders. Epigenetic dysregulation due to adverse events in early life is one of the major factors in generating the symptoms of IBS in adulthood.
Download or read book The Amphipathic Helix written by Richard M. Epand and published by CRC Press. This book was released on 1993-07-09 with total page 422 pages. Available in PDF, EPUB and Kindle. Book excerpt: The Amphipathic Helix is a comprehensive volume discussing amphipathic helices in systems as diverse as serum lipoproteins, lung surfactant, cytotoxic peptides, ion channels, mitochondrial targeting, peptide hormones, G proteins, T-cell recognition, DNA binding proteins, and antifreeze proteins. The book also includes general introductory material that defines amphipathic helices, discusses methods to identify amphipathic helical segments from the amino acid sequence of a protein, illustrates how amphipathic helices can be used in the de novo design of peptide and protein structures, and describes how these helices stabilize protein structures. There is also a section on techniques to determine helix orientation in a membrane environment using polarized attenuated total reflection infrared spectroscopy or solid state NMR spectroscopy. Recent developments on all these topics have been discussed by leading experts in this reference for researchers and students in biochemistry, biophysics, and pharmacology.
Download or read book Textbook of Receptor Pharmacology written by John C. Foreman and published by CRC Press. This book was released on 2010-09-10 with total page 314 pages. Available in PDF, EPUB and Kindle. Book excerpt: For the past four decades, University College London has offered a renowned course on receptor pharmacology. Originating from this course, the perennially bestselling Textbook of Receptor Pharmacology has presented in-depth coverage of this rapidly expanding area of research. This third edition continues to combine current understanding of classica
Download or read book The Endothelium written by Michel Félétou and published by Morgan & Claypool Publishers. This book was released on 2011 with total page 309 pages. Available in PDF, EPUB and Kindle. Book excerpt: The endothelium, a monolayer of endothelial cells, constitutes the inner cellular lining of the blood vessels (arteries, veins and capillaries) and the lymphatic system, and therefore is in direct contact with the blood/lymph and the circulating cells. The endothelium is a major player in the control of blood fluidity, platelet aggregation and vascular tone, a major actor in the regulation of immunology, inflammation and angiogenesis, and an important metabolizing and an endocrine organ. Endothelial cells controls vascular tone, and thereby blood flow, by synthesizing and releasing relaxing and contracting factors such as nitric oxide, metabolites of arachidonic acid via the cyclooxygenases, lipoxygenases and cytochrome P450 pathways, various peptides (endothelin, urotensin, CNP, adrenomedullin, etc.), adenosine, purines, reactive oxygen species and so on. Additionally, endothelial ectoenzymes are required steps in the generation of vasoactive hormones such as angiotensin II. An endothelial dysfunction linked to an imbalance in the synthesis and/or the release of these various endothelial factors may explain the initiation of cardiovascular pathologies (from hypertension to atherosclerosis) or their development and perpetuation. Table of Contents: Introduction / Multiple Functions of the Endothelial Cells / Calcium Signaling in Vascular Cells and Cell-to-Cell Communications / Endothelium-Dependent Regulation of Vascular Tone / Conclusion / References
