Download or read book Functional Characterization of Protease activated Receptor 1 Palmitoylation in Receptor Signaling and Trafficking written by Isabel Canto Cordova and published by . This book was released on 2014 with total page 172 pages. Available in PDF, EPUB and Kindle. Book excerpt: G protein-coupled receptors (GPCRs) are the largest family of signaling receptors that respond to diverse stimuli and regulate many physiological responses. GPCRs elicit their cellular responses by coupling to distinct subtypes of heterotrimeric G-proteins composed of G[alpha] and G[beta][gamma] subunits. Activated GPCRs undergo conformational changes that allow the receptor to exchange GDP for GTP on the G[alpha] subunit, which induces dissociation from the [beta][gamma] subunits and subsequent downstream signaling. Protease-activated receptor-1 (PAR1) is a member of a family of GPCRs that are proteolytically activated. PAR1 is a receptor for the coagulant protease thrombin, and is capable of coupling to multiple G-protein subtypes to elicit various cellular responses; however, the mechanisms that regulate this selectivity are not well understood. Palmitoylation is a post-translational modification that many GPCRs possess, and is defined as the addition of palmitate, a 16 carbon fatty acid, to a cysteine residue via a thioester linkage. Many GPCRs are palmitoylated on their C-terminal tails, but the role of this modification differs based on the GPCR being examined. In this dissertation, I examined the role of palmitoylation in PAR1 signaling and trafficking. I defined the sites of PAR1 palmitoylation to occur on conserved C-tail cysteine residues C387 and C388. I discovered that palmitoylation is important for other PAR1 post-translational modifications, specifically phosphorylation and ubiquitination. I also show that palmitoylation of PAR1 regulates the accessibility of a nearby tyrosine-based sorting motif to the adaptor-protein complex-2 (AP-2) and -3 (AP-3), which controls receptor internalization and degradation. Additionally, palmitoylation appears to be important for the regulation of selective PAR1-induced signaling pathways such as G[alpha]12/13 -induced RhoA activation, G[alpha]i coupling, and thrombin-stimulated p38 MAPK signaling pathways. However, thrombin-induced G[alpha]q-mediated phosphoinositide hydrolysis and ERK1/2 activation are unperturbed in the absence of PAR1 palmitoylation. Taken together, the studies summarized in this dissertation highlight the relevance of palmitoylation for PAR1 function, and suggest that palmitoylation governs a C-tail conformation that is important for accessibility of other proteins such as ligases, kinases, adaptor proteins, and G-proteins, ultimately regulating PAR1 signaling and trafficking.
Download or read book Characterization of Protease activated Receptor 4 Trafficking and Heterodimerization in Modulating Receptor Signaling written by Thomas Horace Smith and published by . This book was released on 2016 with total page 140 pages. Available in PDF, EPUB and Kindle. Book excerpt: G protein-coupled receptors (GPCRs) are transmembrane proteins that allow cells to respond to extracellular stimuli. GPCR activation occurs when a ligand binds to the extracellular portion of the receptor. The ligand-bound receptor undergoes a conformational change that allows the intracellular domain of the receptor to engage and activate signaling effectors. The protease-activated receptors (PARs) are a family of GPCRs that are activated by proteases such as thrombin. Unlike traditional GPCRs, which can return to their inactive state after signaling, PARs are irreversibly activated. Therefore, the eventual fate of an activated PAR is degradation. The internalization and endocytic sorting of PARs play key roles in their signal regulation. Trafficking has been well-characterized for PAR1, the prototypical thrombin receptor. PAR4 was the last of the four thrombin receptor to be discovered, and has in large part been relatively under-studied. Recent studies have shown that PAR4 plays distinct roles that differ from those of PAR1, and as such may represent a potential drug target. Thus, understanding the mechanisms that regulate PAR4 signal regulation is important. In this dissertation, I characterized the role that trafficking and heterodimerization play in regulating PAR4 signaling. I found that adaptor-protein complex-2 (AP-2) is a key mediator of PAR4 agonist-induced internalization, and that AP-2 binds to intracellular loop 3 (ICL3) of PAR4. Disruption of PAR4 internalization resulted in enhanced and prolonged ERK1/2 activation, suggesting that endocytosis may mediate PAR4 signal attenuation. I also characterized the role of heterodimerization with the puringeric receptor P2Y12 in modulating PAR4 signaling. Previous studies had demonstrated that PAR4 and P2Y12 coordinate [beta]-arrestin-dependent Akt activation. My work strongly suggests that PAR4 and P2Y12 physically associate basally and co-internalize in response to activation of PAR4. I also demonstrate that [beta]-arrestin is recruited to the co-internalized PAR4-P2Y12 complex. In contrast to the effect on ERK1/2 activation, disruption of PAR4 internalization diminished Akt activation. Taken together, the studies summarized in this dissertation highlight the importance of PAR4 internalization in modulating activity of functionally and spatially distinct signaling pathways.
Download or read book Serotonin Receptors in Neurobiology written by Amitabha Chattopadhyay and published by CRC Press. This book was released on 2007-05-17 with total page 230 pages. Available in PDF, EPUB and Kindle. Book excerpt: A number of developments spanning a multitude of techniques makes this an exciting time for research in serotonin receptors. A comprehensive review of the subject from a multidisciplinary perspective, Serotonin Receptors in Neurobiology is among the first books to include information on serotonin receptor knockout studies. With contributions from l
Download or read book Platelets written by Alan D. Michelson and published by Academic Press. This book was released on 2019-03-07 with total page 1268 pages. Available in PDF, EPUB and Kindle. Book excerpt: Platelets, Fourth Edition, integrates the entire field of platelet biology, pathophysiology, and clinical medicine with contributions from 142 world experts from 18 countries. This award-winning reference provides clear presentations by basic scientists on the cellular, molecular, and genetic mechanisms of platelets and the role of platelets in thrombosis, hemorrhage, inflammation, antimicrobial host defense, wound healing, angiogenesis and cancer. It also provides start-of-the-art presentations by hematologists, cardiologists, stroke physicians, blood bankers, pathologists and other clinicians on platelet function testing, disorders of platelet numbers and function, antiplatelet therapy and therapy to increase platelet numbers and/or function. Since the publication of the Third Edition of Platelets, there has been a rapid expansion of knowledge in both basic biology of platelets and the clinical approach to platelet-related diseases. This Fourth Edition of Platelets draws all this information into a single, comprehensive and authoritative resource. Comprehensive and definitive source of state-of-the-art knowledge about platelets Integrates the entire field of platelet biology, pathophysiology, and clinical medicine Written for clinicians, pathologists and scientists by 142 world-renowned experts from 18 countries Completely revised and updated, with 11 new chapters on topics such as platelet glycobiology, the platelet transcriptome, platelet inhibitory receptors, platelet function testing in clinical research trials, therapeutic platelet-rich plasma in wound healing, and new antiplatelet drugs Full color textbook with over 250 illustrations and 15,000 references
Download or read book Fas Signaling written by Harald Wajant and published by Springer Science & Business Media. This book was released on 2007-04-03 with total page 169 pages. Available in PDF, EPUB and Kindle. Book excerpt: Fas Signaling is focused on the signaling mechanisms and biology of the prototypic death receptor Fas, also called CD95 or APO-1. The chapters of this book cover, besides the well recognized apoptosis-related functions of Fas, its emerging role as a proinflammatory cytokine and as an inducer of alternative forms of cell death. Fas Signaling aims to provide the reader with an up-to-date survey of the various aspects of Fas biology and the open questions of the field are addressed. This title is intended for Ph.D and post-doctoral students starting to work in the field, but is also useful for everyone with an interest in the biology of this exciting molecule.
Download or read book Matrix Metalloproteinases and TIMPs written by J. F. Woessner and published by . This book was released on 2023 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: This study covers the sequence information, three-dimensional structures, activation, protein substrates, specificity requirements, inhibition, and biological roles of identified MMPs.
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
Download or read book Cumulated Index Medicus written by and published by . This book was released on 1995 with total page 1732 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Protein Phosphorylation in Human Health written by Cai Huang and published by BoD – Books on Demand. This book was released on 2012-09-06 with total page 482 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.
Download or read book Receptor like Kinases in Plants written by Frans Tax and published by Springer Science & Business Media. This book was released on 2012-01-21 with total page 314 pages. Available in PDF, EPUB and Kindle. Book excerpt: Sequencing projects have revealed the presence of at least several hundred receptor kinases in a typical plant genome. Receptor kinases are therefore the largest family of primary signal transducers in plants, and their abundance suggests an immense signaling network that we have only just begun to uncover. Recent research findings indicate that individual receptor kinases fulfill important roles in growth and development, in the recognition of pathogens and symbionts or, in a few examples, in both growth and defense. This volume will focus on the roles of receptor kinases, their signaling pathways, and the ways in which these important signaling proteins are regulated.
Download or read book Biomolecular Interactions Part B written by and published by Academic Press. This book was released on 2022-05-25 with total page 366 pages. Available in PDF, EPUB and Kindle. Book excerpt: Biomolecular Interactions: Part A, Volume 169, the latest release in the Methods in Cell Biology series, highlights new advances in the field, with this new volume presenting interesting chapters on a variety of timely topics, including Emerging Mechanisms of Targeted Protein Degradation by Molecular Glues, Design and use of programmable DNA Hydrogels, Oligomerization of membrane receptors: Approaches to measure in live cells, Interactions of alpha-synuclein with biomolecules, Gel-electrophoresis based method for biomolecular interaction, Recombinant centrosome expression in bacterial system, Reconstituting CCL5-CCR5 complex for structural and mechanistic analysis, Protein engineering and design in ion channel receptors, and much more. Provides the authority and expertise of leading contributors from an international board of authors Presents the latest release in the Methods in Cell Biology series Updated release includes the latest information on biomolecular interactions instead of protein-protein interactions
Download or read book Magnesium in the Central Nervous System written by Robert Vink and published by University of Adelaide Press. This book was released on 2011 with total page 354 pages. Available in PDF, EPUB and Kindle. Book excerpt: The brain is the most complex organ in our body. Indeed, it is perhaps the most complex structure we have ever encountered in nature. Both structurally and functionally, there are many peculiarities that differentiate the brain from all other organs. The brain is our connection to the world around us and by governing nervous system and higher function, any disturbance induces severe neurological and psychiatric disorders that can have a devastating effect on quality of life. Our understanding of the physiology and biochemistry of the brain has improved dramatically in the last two decades. In particular, the critical role of cations, including magnesium, has become evident, even if incompletely understood at a mechanistic level. The exact role and regulation of magnesium, in particular, remains elusive, largely because intracellular levels are so difficult to routinely quantify. Nonetheless, the importance of magnesium to normal central nervous system activity is self-evident given the complicated homeostatic mechanisms that maintain the concentration of this cation within strict limits essential for normal physiology and metabolism. There is also considerable accumulating evidence to suggest alterations to some brain functions in both normal and pathological conditions may be linked to alterations in local magnesium concentration. This book, containing chapters written by some of the foremost experts in the field of magnesium research, brings together the latest in experimental and clinical magnesium research as it relates to the central nervous system. It offers a complete and updated view of magnesiums involvement in central nervous system function and in so doing, brings together two main pillars of contemporary neuroscience research, namely providing an explanation for the molecular mechanisms involved in brain function, and emphasizing the connections between the molecular changes and behavior. It is the untiring efforts of those magnesium researchers who have dedicated their lives to unraveling the mysteries of magnesiums role in biological systems that has inspired the collation of this volume of work.
Download or read book Molecular Aspects of G Protein coupled Receptors written by Francisco Ciruela and published by Nova Publishers. This book was released on 2008 with total page 328 pages. Available in PDF, EPUB and Kindle. Book excerpt: In the recent years, studies based on two-hybrid screens, proteomic, biochemical and cell biology approaches, have shown that intracellular domains of G protein-coupled receptors (GPCR) or heptaspanning membrane receptors (HSMRs) interact with intracellular proteins. These interactions are the basis of a protein network associated to these receptors which includes scaffolding proteins containing one or several PDZ (post-synaptic density-95, discs large, zona occludens-1) domains, signalling proteins and proteins of the cytoskeleton. The present book is focused on the emerging evidence for interactions of G protein-coupled receptors with scaffolding, cytoskeletal and signalling proteins that will play a role in the targeting, anchoring and functioning of these receptors in the plasma membrane, thus contributing to cell development and plasticity.
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 Activation of Viruses by Host Proteases written by Eva Böttcher-Friebertshäuser and published by Springer. This book was released on 2018-05-22 with total page 337 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book will give an overview on viruses undergoing proteolytic activation through host proteases. The chapters will be organized in three themed parts, the first part describing respective viruses and their characteristics in detail. In the second part the molecular and cellular biology of the proteases involved as well as their physiological functions will be further explored. The third part will contain a chapter on protease inhibitors that are promising tools for antiviral therapy. This book will engage scholars in virology and medical microbiology as well as researchers with an interest in enzymology and protein structure and function relationship.
Download or read book Activity Based Protein Profiling written by Benjamin F. Cravatt and published by Springer. This book was released on 2019-01-25 with total page 417 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume provides a collection of contemporary perspectives on using activity-based protein profiling (ABPP) for biological discoveries in protein science, microbiology, and immunology. A common theme throughout is the special utility of ABPP to interrogate protein function and small-molecule interactions on a global scale in native biological systems. Each chapter showcases distinct advantages of ABPP applied to diverse protein classes and biological systems. As such, the book offers readers valuable insights into the basic principles of ABPP technology and how to apply this approach to biological questions ranging from the study of post-translational modifications to targeting bacterial effectors in host-pathogen interactions.
Download or read book Tetraspanins written by Fedor Berditchevski and published by Springer Science & Business Media. This book was released on 2013-03-20 with total page 422 pages. Available in PDF, EPUB and Kindle. Book excerpt: Tetraspanin proteins have recently emerged as a new class of modulators of various processes involving cell surface receptors, including cell migration and invasion, host immune responses, cell-cell fusion, and viral infection. The book summarises recent advances in the fields of biology in which the role of tetraspanins have been established and also covers the molecular evolution of the tetraspanin superfamily and structural aspects of the organisation of tetraspanin microdomains.
