Download or read book Regulation of Non canonical MAP Kinase Signaling written by Gergory Omerza and published by . This book was released on 2016 with total page 436 pages. Available in PDF, EPUB and Kindle. Book excerpt: Mitogen activated protein kinases (MAPKs) are signaling enzymes that control diverse processes in eukaryotic cells including proliferation, differentiation, and development. Many MAPKs are activated through well-studied canonical signaling pathways in which a MAPK kinase phosphorylates a T-X-Y motif in the activation loop of the MAPK. However, MAPKs can also be activated by non-canonical mechanisms. Smk1 is a meiosis-specific MAPK in the yeast S. cerevisiae that controls spore wall morphogenesis. The Smk1 pathway provides a model system to interrogate mechanisms of non-canonical MAPK signaling in the context of a developmental program. Previous genetic studies identified CAK1, AMA1 , IME2 and SSP2 as genes that regulate Smk1. Cak1 is a cyclin-dependent kinase (CDK)-activating kinase. Ama1 is a meiosis-specific targeting factor of the APC/C E3 ubiquitin ligase that controls exit from meiosis II (MII). Ime2 is a meiosis-specific CDK-like kinase. Ssp2 is a meiosis-specific protein required for spore morphogenesis, whose biochemical function has not previously been described. In this thesis we provide evidence for a novel spatiotemporal regulatory mechanism in which Cak1 phosphorylates Smk1 on its activation-loop T (T207) as the meiotic divisions are taking place. Smk1 autophosphorylates its activation-loop Y (Y209) as Ssp2 binds Smk1 at membranes that surround haploid products (prospore membranes; PSMs) during exit from meiosis II. Ssp2/Smk1 complex formation is regulated through multiple mechanisms, preventing premature MAPK activity. First, although both SMK1 and SSP2 are transcriptionally induced as cells enter meiosis I (MI), SMK1 mRNA is translated almost immediately, while SSP2 mRNA is translationally repressed until Ime2 triggers its derepression at MII. Next, Ssp2 localizes to PSMs, but inhibitory phosphates prevent it from binding Smk1. These phosphates are removed during meiotic exit, as PSMs close around each meiotic product in a step that requires Ama1. Finally, dephosphorylated Ssp2 binds Smk1, inducing RRM-like domains in the C-terminus of Ssp2 bind Smk1. Taken together, this work has defined novel mechanisms for spatiotemporally regulating the smk1 MAPK during meiotic development.

Download or read book Spatiotemporal Regulation of Non canonical MAPK Signaling written by Chong Wai Tio and published by . This book was released on 2016 with total page 454 pages. Available in PDF, EPUB and Kindle. Book excerpt: Mitogen activated protein kinases (MAPKs) are conserved signaling enzymes that regulate an array of essential cellular processes in eukaryotic cells. Canonical MAPK signaling is defined by a three-tier kinase module in which a dual-specificity MAPK kinase phosphorylates the T-X-Y motif in the activation loop of the MAPK. MAPKs can also be activated by non-canonical signaling pathways, yet relatively little is known about these pathways and how they are controlled. Smk1 is a non-canonically activated MAPK in the yeast S. cerevisiae that is expressed specifically in meiotic cells and controls spore wall morphogenesis. The Smk1 pathway represents an excellent model to study mechanisms that control non-canonical MAPKs in the context of a developmental program. Prior studies demonstrated that the activation loop T in Smk1 (T207) is phosphorylated by the CDK activating kinase, Cak1, and the activation-loop Y (Y209) is autophosphorylated in an intramolecular reaction that requires a meiosis-specific protein, Ssp2. Data presented in this thesis show that Smk1 is almost immediately phosphorylated by Cak1 on T207 when it is produced during meiosis I, yet this early form of Smk1 is inactive and Smk1 is not activated until later in the program. Activation occurs specifically at membranes that surround incipient haploids termed prospore membranes (PSMs) in a switch-like fashion as cells exit meiosis II. This tight spatiotemporal control of Smk1 activation is achieved through Ssp2. The temporal control is achieved by a meiosis-specific translational regulatory pathway that represses SSP2 mRNA until anaphase II, while spatial control is achieved by an amino-terminal domain of Ssp2 that is both necessary and sufficient for PSM targeting. Kinase activation is achieved by Ssp2's carboxy-terminal kinase activating domain (KAD) that activates catalysis by directly binding to Smk1. Ssp2 binding also triggers Smk1 autophosphorylation of Y209. Heterologous expression/reconstitution experiments demonstrate that phosphorylation of SMK1-T207 and Y209 increases Ssp2/Smk1 catalytic activity. These studies also identify Y-X-X-X-S/T-P as the unique phosphorylation consensus motif of Smk1. Together, these data dafine a novel mechanism of non-canonical MAPK activation and provide new insights into how MAPKs are spatiotemporally regulated in the context of a developmental program.

Download or read book Regulation of Tissue Responses The TWEAK Fn14 Pathway and other TNF TNFR Superfamily Members that Activate Noncanonical NFkB Signaling written by Linda C. Burkly and published by Frontiers Media SA. This book was released on 2016-01-21 with total page 203 pages. Available in PDF, EPUB and Kindle. Book excerpt: The immune system mediates tissue responses under both physiological and pathological conditions, impacting the inflammatory, fibrogenic and regenerative components. In addition to various leukocyte subsets, it is now recognized that epithelial, endothelial and other non-hematopoietic tissue cell types actively contribute to the interplay shaping tissue responses. Further understanding the molecular pathways and mechanisms mediating these tissue responses is of great interest. In the past decade, TNF-like weak inducer of apoptosis (TWEAK) and its receptor, FGF-inducible molecule-14 (Fn14), members of the TNF/TNFR superfamily, have emerged as a prominent molecular axis regulating tissue responses. Generally leukocyte-derived, TWEAK signals through Fn14 which is highly induced in injured and diseased tissues on the surface of parenchymal, stromal and progenitor cells, thereby orchestrating a host of tissue-shaping responses, including inflammation, angiogenesis, cell proliferation or death, and the regulation of progenitor cells. Compelling preclinical results indicate that whereas transient TWEAK/Fn14 activation promotes productive tissue responses after acute injury, excessive or persistent TWEAK/Fn14 activation drives pathological tissue responses, leading to progressive damage and degeneration in target organs of injury, autoimmune and inflammatory diseases and cancer. Given that the highly inducible pattern of Fn14 expression is well conserved between mouse and man, the role of TWEAK/Fn14 in human disease is an area of intense investigation. Recent findings have also begun to shed light on how the TWEAK/Fn14 pathway fits into the immune network, interplaying with other well-established pathways, including TNFa, IL-17, IL-13 and TGFb, in regulating tissue responses. The noncanonical nuclear factor kB (NF?B) pathway plays a role in immunity and disease pathologies and appears to be activated by only a subset of TNF/ TNFR superfamily members. Of the various signaling pathways downstream of TWEAK/Fn14, particular attention has been placed on the noncanonical NF?B pathway given that given that TWEAK induces acute activation of canonical NF?B but prolonged activation of noncanonical pathway. Thus dovetailing of the TWEAK/Fn14 axis with noncanonical NF?B pathway activation may be a key mechanism underlying tissue responses. Also of great interest is a deeper understanding of where, when and how tissue responses are regulated by other TNF/ TNFR superfamily members that can signal through noncanonical NF?B. This Research Topic issue will cover: 1. TWEAK/Fn14 pathway biology, role in tissue responses, injury, and disease pathogenesis 2. Role of noncanonical NFkB signaling cascade in tissue responses 3. Translational studies of relevance of TWEAK/Fn14 and noncanonical NFkB in human disease 4. Other TNF superfamily members’ signaling through noncanonical NFkB in the regulation of tissue responses 5. Reviews and Perspectives on the above

Download or read book Stress Activated Protein Kinases written by Francesc Posas and published by Springer Science & Business Media. This book was released on 2008-01-24 with total page 322 pages. Available in PDF, EPUB and Kindle. Book excerpt: In this book leading researchers in the field discuss the state-of-the-art of many aspects of SAPK signaling in various systems from yeast to mammals. These include various chapters on regulatory mechanisms as well as the contribution of the SAPK signaling pathways to processes such as gene expression, metabolism, cell cycle regulation, immune responses and tumorigenesis. Written by international experts, the book will appeal to cell biologists and biochemists.

Download or read book Canonical and Non canonical Regulation of AMP activated Protein Kinase written by Francesca Romana Auciello and published by . This book was released on 2015 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book MAP Kinase Signaling Protocols written by Rony Seger and published by Springer Science & Business Media. This book was released on 2008-02-03 with total page 335 pages. Available in PDF, EPUB and Kindle. Book excerpt: Mitogen-activated protein kinase (MAPK) signaling cascades are a group of protein kinases that play a central role in the intracellular transmission of extracellular signals. These cascades operate as major lines of communication within a complicated signaling network that regulates many cellular processes, including proliferation, differentiation, development, stress response, and apoptosis. More than 15,000 papers on MAPKs have been published over the past few years, with the number of publications increasing each year. More and more laboratories embark on the study of MAPK cascades in many d- tinct cellular systems and in particular their role in disease. Future challenges in the study of MAPK cascades remain in understa- ing the role of the various components and isoforms of the cascades in the multiple critical functions that they regulate in the whole organism, as well as the diseases caused by their malfunction. Data from gene-disrupted mice s- gest that inhibition of the MAPK cascades may have serious consequences on the development and growth of the animals. For example, targeted deletion of MEK1 is lethal, owing to developmental problems of placental vasculature and abnormal fibroblast migration. This lethality occurs in spite of the normal expression of MEK2, indicating that although the two MEK isoforms are apparently similar, they do have distinct functions, at least during embryog- esis. The ERK cascade was also shown to play a central role in brain function and in learning and memory.

Download or read book Non canonical Cyclic Nucleotides written by Roland Seifert and published by Springer. This book was released on 2017-04-28 with total page 379 pages. Available in PDF, EPUB and Kindle. Book excerpt: The cyclic purine nucleotides 3’,5’-cAMP and 3’,5’-cGMP are well-established second messengers. cGMP has recently been covered in a volume of the Handbook of Experimental Pharmacology (volume 191). In addition to 3’,5’-cAMP and 3’,5’-cGMP, so-called non-canonical cyclic nucleotides exist. These comprise the cyclic pyrimidine nucleotides 3’,5’-cCMP and 3’,5’-cUMP, the purine nucleotide 3’,5’-cIMP, the 2’,3’-nucleoside monophosphates and cyclic dinucleotides. In this volume of the Handbook of Pharmacology, word-leading experts in the field summarize our current knowledge on these non-canonical cyclic nucleotides, discuss open questions, future research directions and the pharmacotherapeutic implications. Special emphasis will be given to the emerging roles of 3’,5’-cCMP and 3’,5’-cUMP as second messengers with regard to generators, effectors, biological functions, inactivation and bacterial toxins. The role of 3’,5’-cIMP as potential second messenger will also be critically discussed. Furthermore, we will consider transport of cyclic nucleotides and their potential role as first messengers. The role of the cyclic dinucleotide cGAMP in the immune system will covered, too. Lastly, the book will present important methodological aspects ranging from mass-spectrometric methods for cyclic nucleotide detection to the synthesis of nucleotide analogs as experimental tools and holistic methods for analysis of cyclic nucleotide effects.

Download or read book Structures Signaling Mechanisms and Functions of Types I and III Interferons written by Ronald L. Rabin and published by Frontiers Media SA. This book was released on 2021-04-23 with total page 133 pages. Available in PDF, EPUB and Kindle. Book excerpt: Dr. Walter receives financial support from Pfizer. The other Topic Editor declares no competing interest with regards to the Research Topic theme.

Download or read book Systems Biology of Transcription Regulation written by Ekaterina Shelest and published by Frontiers Media SA. This book was released on 2016-09-09 with total page 191 pages. Available in PDF, EPUB and Kindle. Book excerpt: Transcription regulation is a complex process that can be considered and investigated from different perspectives. Traditionally and due to technical reasons (including the evolution of our understanding of the underlying processes) the main focus of the research was made on the regulation of expression through transcription factors (TFs), the proteins directly binding to DNA. On the other hand, intensive research is going on in the field of chromatin structure, remodeling and its involvement in the regulation. Whatever direction we select, we can speak about several levels of regulation. For instance, concentrating on TFs, we should consider multiple regulatory layers, starting with signaling pathways and ending up with the TF binding sites in the promoters and other regulatory regions. However, it is obvious that the TF regulation, also including the upstream processes, represents a modest portion of all processes leading to gene expression. For more comprehensive description of the gene regulation, we need a systematic and holistic view, which brings us to the importance of systems biology approaches. Advances in methodology, especially in high-throughput methods, result in an ever-growing mass of data, which in many cases is still waiting for appropriate consideration. Moreover, the accumulation of data is going faster than the development of algorithms for their systematic evaluation. Data and methods integration is indispensable for the acquiring a systematic as well as a systemic view. In addition to the huge amount of molecular or genetic components of a biological system, the even larger number of their interactions constitutes the enormous complexity of processes occurring in a living cell (organ, organism). In systems biology, these interactions are represented by networks. Transcriptional or, more generally, gene regulatory networks are being generated from experimental ChIPseq data, by reverse engineering from transcriptomics data, or from computational predictions of transcription factor (TF) – target gene relations. While transcriptional networks are now available for many biological systems, mathematical models to simulate their dynamic behavior have been successfully developed for metabolic and, to some extent, for signaling networks, but relatively rarely for gene regulatory networks. Systems biology approaches provide new perspectives that raise new questions. Some of them address methodological problems, others arise from the newly obtained understanding of the data. These open questions and problems are also a subject of this Research Topic.

Download or read book The Dopamine Receptors written by Kim Neve and published by Springer Science & Business Media. This book was released on 2009-12-01 with total page 650 pages. Available in PDF, EPUB and Kindle. Book excerpt: As sites of action for drugs used to treat schizophrenia and Parkinson’s disease, dopamine receptors are among the most validated drug targets for neuropsychiatric disorders. Dopamine receptors are also drug targets or potential targets for other disorders such as substance abuse, depression, Tourette’s syndrome, and attention deficit hyperactivity disorder. Updated from the successful first edition, "The Dopamine Receptors" serves as a reference work on dopamine receptors while also highlighting the areas of research that are most active today. To achieve this goal, authors have written chapters that set a broad area of research in its historical context, rather than focusing on the research output of their own laboratories.

Download or read book Regulation of Immunity by Non Immune Cells written by Kenji Kabashima and published by Frontiers Media SA. This book was released on 2021-11-08 with total page 130 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Innovative Medicine written by Kazuwa Nakao and published by Springer. This book was released on 2015-10-13 with total page 330 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book is devoted to innovative medicine, comprising the proceedings of the Uehara Memorial Foundation Symposium 2014. It remains extremely rare for the findings of basic research to be developed into clinical applications, and it takes a long time for the process to be achieved. The task of advancing the development of basic research into clinical reality lies with translational science, yet the field seems to struggle to find a way to move forward. To create innovative medical technology, many steps need to be taken: development and analysis of optimal animal models of human diseases, elucidation of genomic and epidemiological data, and establishment of “proof of concept”. There is also considerable demand for progress in drug research, new surgical procedures, and new clinical devices and equipment. While the original research target may be rare diseases, it is also important to apply those findings more broadly to common diseases. The book covers a wide range of topics and is organized into three complementary parts. The first part is basic research for innovative medicine, the second is translational research for innovative medicine, and the third is new technology for innovative medicine. This book helps to understand innovative medicine and to make progress in its realization.

Download or read book Progress in Heritable Soft Connective Tissue Diseases written by Jaroslava Halper and published by Springer Science & Business Media. This book was released on 2014-01-18 with total page 246 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume is a reference handbook focusing on diseases like Marfan syndrome, Ehlers-Danlos syndrome, Loeys-Dietz syndrome and other heritable soft connective tissue diseases. The book presents detailed information for both basic scientists and for clinicians seeing patients. It is also a stepping stone for new investigations and studies that goes beyond the facts about the composition and biochemistry of the connective tissue and extracellular matrix, as the authors connect individual components to specific aspects of various soft tissue disorders and to the actual or potential treatment of them. Progress in Heritable Soft Connective Tissue Diseases features very prominent physicians and scientists as contributors who bring their most recent discoveries to the benefit of readers. Their expertise will help clinicians with proper diagnosis of sometimes elusive and uncommon heritable diseases of soft connective tissues. This book also offers an update on the pathophysiology of these diseases, including an emphasis on unifying aspects such as connections between embryonic development of the different types of connective tissues and systems, and the role of TGF-beta in development and physiology of soft tissues. This new set of data explains, at least in part, why many of these disorders are interconnected, though the primary pathophysiological events, such as gene mutations, may be different for each disorder.

Download or read book Transcription Regulation Brain Development and Homeostasis A Finely Tuned and Orchestrated Scenario in Physiology and Pathology Volume II written by Estela Maris Muñoz and published by Frontiers Media SA. This book was released on 2023-10-03 with total page 169 pages. Available in PDF, EPUB and Kindle. Book excerpt: A finely tuned regulation of gene expression is essential for shaping the nervous system and for maintaining its homeostasis throughout life. Disruptions in gene regulation can impact brain development and physiology in ways that contribute to diverse pathologies. The master orchestrators of gene activity in the nucleus are transcription factors, proteins that recognize and bind to specific DNA motifs in regulatory regions and drive changes in gene expression. Transcription factors act with the help of other co-factor proteins, including components of the Mediator complex, histone modifying enzymes, chromatin modelers, and DNA methylases. In addition, transcription factor activity in the nervous system can be modulated by extracellular signals, including growth factors, hormones, neuropeptides and neurotransmitters that activate specific receptors and intracellular transduction pathways. An in-depth understanding of the mechanisms of transcription regulation is needed in order to better describe how each element, from genes to cells, defines and maintains identities and functionalities in the healthy and diseased brain. This Research Topic is oriented to developing an integrative view about transcription regulation within the nervous system, focusing on developmental and homeostatic processes, dysregulation in functionality and expression levels and consequent associated pathologies such as neurodevelopmental disorders, brain tumors, and neurodegenerative diseases. Transcription regulation investigations will specifically focus on transcription factors that belong to the bHLH (e.g. NeuroD), homeobox (e.g. Islet, Pax, Rax, and Lhx) and CREB families, and on their roles over defined nervous system areas: cerebral cortex, thalamic and hypothalamic areas, interacting with the developing brain.

Download or read book Encyclopedia of Inflammatory Diseases written by and published by Birkhäuser. This book was released on 2016-09-15 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Inflammation has become one of the most exciting and rewarding areas of medical research. Recent years have seen a revolution in our understanding of how blood and tissue cells interact and of the intracellular mechanisms controlling their activation. This has revealed the underlying inflammatory pathology of many diseases and provided multiple new targets for anti-inflammatory and immunomodulatory therapy. The Encyclopedia of Inflammatory Diseases will cover the following areas: Inflammatory Processes and Cells Inflammatory Diseases Mediators of Inflammation Pharmacology of Inflammation Since inflammatory diseases and their therapy cover a broad range of scientific and medical fields, the encyclopedia will be co-edited by four international experts, a clinician and three researchers from the disciplines of immunology, biochemistry, and pharmacology, in this way providing students, basic and clinical scientists and practitioners in academia, hospitals and industry with valuable interlinked information. This living project will serve as a reliable and comprehensive data pool for everybody working in inflammation research. Owing to its dynamic nature, it will grow with time and future editions, becoming an indispensible source of information for academia, clinical practitioners and industry.

Download or read book Reactive Oxygen Species ROS Nanoparticles and Endoplasmic Reticulum ER Stress Induced Cell Death Mechanisms written by Loutfy H. Madkour and published by Academic Press. This book was released on 2020-06-27 with total page 782 pages. Available in PDF, EPUB and Kindle. Book excerpt: Reactive Oxygen Species (ROS), Nanoparticles, and Endoplasmic Reticulum (ER) Stress-Induced Cell Death Mechanisms presents the role of ROS?mediated pathways cellular signaling stress, endoplasmic reticulum (ER) stress, oxidative stress, oxidative damage, nanomaterials, and the mechanisms by which metalloids and nanoparticles induce their toxic effects. The book covers the ecotoxicology of environmental heavy metal ions and free radicals on macromolecules cells organisms, heavy metals?induced cell responses, oxidative stress, the source of oxidants, and the roles of ROS, oxidative stress and oxidative damage mechanisms. It also examines the nanotoxicity, cytotoxicity and genotoxicity mechanisms of nanomaterials and the effects of nanoparticle interactions. Antioxidant defense therapy and strategies for treatment round out the book, making it an ideal resource for researchers and professional scientists in toxicology, environmental chemistry, environmental science, nanomaterials and the pharmaceutical sciences. Covers the ecotoxicology of environmental heavy metal ions and the interactions between specific heavy metals?induced cell responses and oxidative stress Provides a better understanding of the mechanism of nanomaterial-induced toxicity as a first defense for hazard prevention Covers recent advances in new nanomedication technologies for the effects of NPs on oxidative stress, ROS and ER stress Discusses the effects of interactions between antioxidant defense therapy, ROS and strategies for treatment

Download or read book Regulation of Organelle and Cell Compartment Signaling written by Ralph A. Bradshaw and published by Academic Press. This book was released on 2011-04-05 with total page 552 pages. Available in PDF, EPUB and Kindle. Book excerpt: This must-have cell signaling title will appeal to researchers across molecular biology, biochemistry, cell biology and genetics. The articles are written and edited by experts in the field and emphasize signaling to and from intracellular compartments including transcriptional responses to cytoplasmic and nuclear signaling events, chromatin remodeling and stress responses, the regulation of endoplasmic reticulum function, control of cell cycle progression and apoptosis and the modulation of the activities of mitochondria and other organelles. Articles written and edited by experts in the field Thematic volume covering regulation of endoplasmic reticulum function, regulation of cell cycle progression, and quality control and assurance in mitochondrion events Up-to-date research on events in membrane proteins and proteins of intracellular matrix