Download or read book Protein Tyrosine Phosphatase Control of Metabolism written by Kendra K. Bence and published by Springer Science & Business Media. This book was released on 2013-08-30 with total page 279 pages. Available in PDF, EPUB and Kindle. Book excerpt: Although phosphorylation of proteins on tyrosine is relatively rare compared to phosphorylation on serine or threonine residues, the past two decades of research into PTP function have led to a great appreciation of the critical role PTPs have in regulating basic cellular processes. Among these important roles is the regulation of cellular signaling pathways related to metabolism. This volume contains chapters which highlight many aspects of PTP function in the context of metabolism. Given the growing obesity and diabetes epidemics in the United States and throughout the world, the desire to identify possible therapeutic targets for treatment of these diseases is a high priority. In many ways, PTPs may be attractive drug targets since they are amenable to targeting with small molecules; however many challenges abound in making PTP inhibitors.
Download or read book Protein Tyrosine Phosphatases written by Lalima G. Ahuja and published by Walter de Gruyter GmbH & Co KG. This book was released on 2018-10-08 with total page 296 pages. Available in PDF, EPUB and Kindle. Book excerpt: Protein tyrosine phosphatases remove phosphates from the phosphotyrosine residues of target proteins and reverse the action of various protein tyrosine kinases. This essential interplay between the opposing actions of protein tyrosine phosphatases and protein tyrosine kinases forms the basis of signaling networks that underlie the cellular workings of human physiology. Initially passed-off as housekeeping genes; these proteins were only acknowledged to maintain a steady background of phosphotyrosine levels in the cell. However, recent progress in studying their role in embryonic development and human disease has established their importance as regulators of signal regulation. Convincing evidence shows the role of mutations in these proteins to cause and/or intensify the severity of various diseases including metabolic and neurological disorders and also cancer. Protein tyrosine phosphatases have slowly, yet convincingly become crucial targets for therapeutic intervention of various human pathophysiologies. This book describes these signaling enzymes using the molecular details of their structure and mechanistic function. Various subtypes of cysteine-based Class I, II, III and the Haloacid dehalogenase related Class IV protein tyrosine phosphatases have been illustrated and explained. The superfamily of proteins is also described vis-a-vis its complimentary protein phosphoserine/phosphoserine phosphatases. Membrane bound receptor forms and the cytosolic non-receptor protein tyrosine phosphatases have been described for their biological function. This book serves as a reference for any reader looking to understand the sequence features, structural elements, molecular mechanism and cellular function of this superfamily of signaling enzymes.
Download or read book Bridging the Gap Between Protein tyrosine Phosphorylation Networks Metabolism and Physiology in Liver specific PTP1b Deletion Mice written by Emily Rae Miraldi and published by . This book was released on 2012 with total page 182 pages. Available in PDF, EPUB and Kindle. Book excerpt: Metabolic syndrome describes a complex set of obesity-related disorders that enhance diabetes, cardiovascular, and mortality risk. Studies of liver-specific protein-tyrosine phosphatase lb (PTPlb) deletion mice (L-PTPlb-/-) suggests that hepatic PTPlb inhibition would mitigate metabolic syndrome progression through amelioration of hepatic insulin resistance, endoplasmic reticulum stress, and whole-body lipid metabolism. However, the network alterations underlying these phenotypes are poorly understood. Mass spectrometry was used to quantitatively discover protein phosphotyrosine network changes in L-PTP lb-/- mice relative to control mice under both normal and high-fat diet conditions. A phosphosite set enrichment analysis was developed to identify numerous pathways exhibiting PTPlb- and diet-dependent phosphotyrosine regulation. Detection of PTP lb-dependent phosphotyrosine sites on lipid metabolic proteins initiated global lipidomics characterization of corresponding liver samples and revealed altered fatty acid and triglyceride metabolism in L-PTPlb-/- mice. Multivariate modeling techniques were developed to infer molecular dependencies between phosphosites and lipid metabolic changes, resulting in quantitatively predictive phenotypic models.
Download or read book Hydrogen Peroxide and Cell Signaling Part B written by and published by Academic Press. This book was released on 2013-07-15 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.
Download or read book Investigations Into the Chemistry of Protein Tyrosine Phosphatase Redox Regulation written by Jason N. LaButti and published by . This book was released on 2009 with total page 148 pages. Available in PDF, EPUB and Kindle. Book excerpt: Transmission of complex intracellular signals, such as those for glucose uptake or proliferation, is often accomplished through the reversible phosphorylation of specific protein tyrosine residues. This reversible phosphorylation serves as a biochemical "rheostat" that alters a protein's functional properties and leads to propagation of the signal. The phosphorylation status of these tyrosine residues, thus transmission of the cellular signal itself, is tightly controlled by the opposing actions of protein tyrosine kinases that catalyze the addition of phosphoryl groups and protein tyrosine phosphatases (PTPs) are cysteine based enzymes that catalyze their removal. Abstraction of these phosphoryl groups, in many cases, serves as an "off switch" to terminate the cellular responses to the extracellular stimulus. PTPs, therefore, play a central role in the regulation of diverse cellular processes including glucose metabolism, cell cycle control and immune responses. Accordingly, small molecules capable of inactivating PTPs through reversible oxidation of their active site cysteine thiolate may find use as therapeutic agents and/or tools for the study of diverse signal transduction pathways. In the body of work presented here we report the chemical properties of a novel PTP redox regulator and develop new methodologies for studying PTP redox regulation.
Download or read book Protein Tyrosine Phosphatases written by Damien Thévenin and published by Springer Nature. This book was released on 2024-01-27 with total page 321 pages. Available in PDF, EPUB and Kindle. Book excerpt: This second edition volume expands on the previous edition with discussions on the latest advancements in protein tyrosine phosphatases (PTP) research used to investigate these essential enzymes and new inhibitors. The new techniques covered in the chapters of this book include studying enzymes in vitro, in cells, and in animal models through proteomics, genomics, and structural biology. Furthermore, new advances in pharmacology and drug design have contributed to the developing novel therapeutics that target PTPs. 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. Cutting-edge and comprehensive, Protein Tyrosine Phosphatases: Methods and Protocols, Second Edition is a valuable resource for both experienced and novel researchers in this field, and will lead to discoveries and accelerated progress in the field of PTP, signal transduction, and drug development.
Download or read book Roles of Protein tyrosine Phosphatases in the Endocrine Pancreas written by Yannan Xi and published by . This book was released on 2013 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Protein-tyrosine phosphatase 1B (PTP1B) and T cell protein-tyrosine phosphatase (TCPTP) are structurally similar cytosolic proteins that are implicated in the regulation of metabolism. PTP1B is an important physiological regulator of glucose homeostasis and energy balance and the role of PTP1B in liver, muscle, and brain has been established. TCPTP is implicated in cytokine-induced pancreatic beta-cell apoptosis and is a candidate gene in type 1 diabetes. However, the roles of PTP1B and TCPTP in pancreatic endocrine function and insulin secretion remain largely unknown. To explore the metabolic role of PTP1B in the pancreas, we generated mice with pancreas-specific PTP1B deletion (panc-PTP1B KO) and fed them chow or high fat diet (HFD) and evaluated their glucose tolerance and insulin secretion. Insulin secretion and biochemical studies were performed on isolated islets and MIN6 cells with knockdown (KD) and reconstituted PTP1B. On regular chow, aged panc-PTP1B KO mice exhibited glucose intolerance compared with controls. HFD led to earlier impairment of glucose tolerance and attenuated glucose-stimulated insulin secretion (GSIS) in panc-PTP1B KO mice. Ex vivo studies demonstrated attenuated GSIS in KO islets and in MIN6 cells with PTP1B knockdown indicating a cell autonomous defect. Mechanistically, basal and glucose-stimulated EphA5 tyrosyl phosphorylation was enhanced in PTP1B deficient islets and in MIN6 cells with PTP1B knockdown. PTP1B reconstitution in KD cells attenuated EphA5 phosphorylation indicating that it is regulated by PTP1B. Moreover, EphA5 mutagenesis revealed that various tyrosine residues differentially modulate insulin secretion, and demonstrated that PTP1B directly regulates insulin secretion, at least in part, via EphA5. Collectively, our studies identify a novel role for pancreatic PTP1B and uncover EphA5 as a physiologically-relevant target for PTP1B. To investigate the metabolic role of TCPTP in pancreatic endocrine function, we generated mice with TCPTP deletion (panc-TCPTP KO). Mice were fed regular chow and HFD and insulin secretion and glucose homeostasis were determined. When fed regular chow diet panc-TCPTP KO mice exhibited comparable glucose tolerance to controls. On the other hand, when challenged with prolonged HFD panc-TCPTP KO mice exhibited impaired glucose tolerance and attenuated glucose-stimulated insulin secretion (GSIS) compared with controls. Ex vivo studies using primary islets demonstrated attenuated GSIS in panc-TCPTP KO islets compared with controls indicating that the effects are cell autonomous. In addition, lentiviral-mediated knockdown of TCPTP in the glucose-responsive MIN6 beta-cells attenuated GSIS while reconstitution of TCPTP restored GSIS to levels compared with controls demonstrating that the effects are directly caused by TCPTP deficiency. Similarly, pharmacological inhibition of TCPTP in Min6 cells attenuated GSIS. At the molecular level we identified STAT 1/3 as direct TCPTP substrates and modulators of its functions in beta-cells. In summary, these studies identify a novel role for TCPTP in insulin secretion and uncover STAT3 as physiologically-relevant target for TCPTP in the pancreas.
Download or read book Molecular Biology of Prostate Cancer written by Manfred Wirth and published by Walter de Gruyter. This book was released on 2013-05-22 with total page 220 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Handbook of Cell Signaling written by Ralph A. Bradshaw and published by Academic Press. This book was released on 2009-11-03 with total page 3188 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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
Download or read book The Metabolic Effects of Novel Protein Tyrosine Phosphatase 1B PTP1B Substrates written by Jesse Bakke and published by . This book was released on 2014 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Protein tyrosine phosphorylation is a covalent modification by protein tyrosine kinases and opposed by protein tyrosine phosphatases (PTPs). Protein phosphorylation is an important regulator of cell signaling pathways in all life forms and aberrant changes of phosphorylated proteins are often associated with diseases, such as cancer and metabolic diseases: obesity and type II diabetes. Importantly, there are over one hundred identified PTPs strictly defined with an active-site signature motif of HCX5R. Out of the one hundred total PTPs, thirty-seven are classical PTPs that are either transmembrane receptor-like PTPs or non-transmembrane PTPs. Protein tyrosine phosphatase 1B (PTP1B) is a non-transmembrane PTP, bound to the cytoplasmic face of endoplasmic reticulum with a C-terminal anchor. PTP1B has several well- known substrates, including the insulin receptor and insulin receptor substrate 1 (IRS1). PTP1B gained popularity as a therapeutic target due to the striking phenotype observed in mice following PTP1B gene deletion. The mice exhibited improved insulin sensitivity and decreased body weight upon high fat diet (HFD) feeding. Through tissue specific deletion, it was revealed that PTP1B has cell/tissue specific roles. Briefly, PTP1B deletion from muscle and liver results in improved insulin sensitivity and neuronal deletion of PTP1B results in resistance to HFD- induced obesity. Adipose specific deletion of PTP1B remains controversial with several contradictory reports; this argues for further work to be done to determine PTP1Bs role within adipose tissue. This dissertation uncovers novel PTP1B substrates in the adipose, syntaxin binding protein 3 (munc18c) and pyruvate kinase M2 (PKM2), and highlights the regulatory role of PTP1B in glucose transporter 4 (GLUT4) externalization as well as glycolytic flux. And surprisingly, PKM2 deficiency results in the emergence of a thermogenic program in white adipocytes.
Download or read book Protein Tyrosine Phosphatases in Cancer written by Benjamin G. Neel and published by Springer. This book was released on 2016-08-05 with total page 362 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book aims to bridge the gap in understanding how protein-tyrosine phosphatases (PTPs), which carry out the reverse reaction of tyrosine phosphorylation, feature in cancer cell biology. The expertly authored chapters will first review the general features of the PTP superfamily, including their overall structure and enzymological properties; use selected examples of individual PTP superfamily members, to illustrate emerging data on the role of PTPs in cancer; and will review the current status of PTP-based drug development efforts. Protein Tyrosine Phosphatases in Cancer,from renowned researchers Benjamin Neel and Nicholas Tonks, is invaluable reading for researchers in oncology, stem cell signaling,and biochemistry.
Download or read book Prokaryotic Metabolism and Physiology written by Byung Hong Kim and published by Cambridge University Press. This book was released on 2019-05-16 with total page 509 pages. Available in PDF, EPUB and Kindle. Book excerpt: Extensive and up-to-date review of key metabolic processes in bacteria and archaea and how metabolism is regulated under various conditions.
Download or read book Inactivation of Protein Tyrosine Phosphatases by Endogenous and Dietary Agents written by Derrick R. Seiner and published by . This book was released on 2009 with total page 133 pages. Available in PDF, EPUB and Kindle. Book excerpt: Protein tyrosine phosphatases are a class of enzymes that control a number of critical signaling pathways inside cells. We have discovered a number of dietary and endogenous agents that are capable of modifying these enzymes, and therefore disrupting signaling pathways inside cells. It is possible that these small molecules are exerting their widely reported biological effect by the modification of protein tyrosine phosphatase activity. This information is critical to our understanding of dietary effect on diseases like diabetes and cancer. In addition to this work, we have explored the chemistry of the most common DNA lesion, the abasic site. We have found it is capable of producing an interstrand crosslink in duplex DNA, when placed in the right sequence context. This work significantly expands our understanding of the toxicity of abasic sites to cells. Furthermore, this work may result in developing novel treatment strategies for cancer.
Download or read book Regulation of Leptin and Insulin Signaling by the T Cell Protein Tyrosine Phosphatase written by Kim Yong Loh and published by . This book was released on 2011 with total page 534 pages. Available in PDF, EPUB and Kindle. Book excerpt: The prevalence of obesity and diabetes are increasing at alarming rates. Both are major health concerns worldwide. Food intake, energy expenditure and hepatic glucose production are regulated by hypothalamic neuronal circuits that respond to peripheral signals including leptin and insulin. Leptin is produced by adipose tissue and acts in the hypothalamus via the JAK2/STAT3 signaling pathway to decrease food intake and increase energy expenditure. It is now also widely appreciated that insulin acts in the hypothalamus to control whole body glucose homeostasis, particularly hepatic glucose production. A key negative regulator of leptin and insulin signaling is the protein tyrosine phosphatase 1B (PTP1B). Hypothalamic PTP1B levels are increased in obese and diabetic models and this is thought to contribute to the development of central leptin and insulin resistance. Neuronal or POMC neuron-specific PTP1B deficiency enhances leptin sensitivity and protects mice from the development of diet-induced obesity whereas PTP1B deficiency in liver and muscle enhances insulin sensitivity through enhanced IR phosphorylation. T-cell protein tyrosine phosphatase (TCPTP) is closely related to PTP1B, sharing a high degree of primary and tertiary structural similarity. Several studies have demonstrated that TCPTP dephosphorylates the IR to attenuate insulin signaling in vitro and in vivo in the liver. Moreover, it has been shown that STAT3, a downstream target of leptin receptor signaling, is a TCPTP substrate in the context of the cell cycle and the control of hepatic gluconeogenesis. However, whether TCPTP may regulate leptin and insulin signaling in the brain remains unknown. Thus, the primary objective of this thesis was to examine the potential role of TCPTP in the regulation of central leptin and insulin signaling. The role of TCPTP in the regulation of central leptin signaling was investigated through the generation and characterisation of neuronal cell-specific TCPTP-deficient mice. Work in this thesis demonstrates that TCPTP is a negative regulator in leptin signaling and that TCPTP dephosphorylates and inactivates STAT3 to attenuate leptin signaling. It was shown that hypothalamic TCPTP levels are increased in obesity consistent with TCPTP contributing to the development of leptin resistance and obesity. Moreover, mice that lack both PTP1B and TCPTP in neuronal cells exhibit additive effects in the attenuation of leptin resistance and diet-induced obesity. Therefore, I propose that elevated hypothalamic PTP1B and TCPTP expression in obesity may together contribute to the development of central leptin resistance. In addition, the role of TCPTP in the regulation of central insulin signaling for the control of hepatic glucose metabolism was assessed through the generation of POMC-neuron specific TCPTP-deficient mice. Mice that lack of TCPTP in POMC neurons exhibit enhanced central insulin signaling coinciding with decreased hepatic glucose production and improved whole body insulin sensitivity. Taken together, the results in this thesis define TCPTP as a negative regulator of central leptin and insulin signaling and highlight the capacity for two phosphatases, TCPTP and PTP1B, to work in concert for the regulation of hormonal signaling in a complex neuronal circuit.
Download or read book Vanadium in Biological Systems written by N.D. Chasteen and published by Springer Science & Business Media. This book was released on 2012-12-06 with total page 226 pages. Available in PDF, EPUB and Kindle. Book excerpt: Over the past several decades, vanadium has increasingly attracted the interest of biologists and chemists. The discovery by Henze in 1911 that certain marine ascidians accumulate the metal in their blood cells in unusually large quantities has done much to stimulate research on the role of vanadium in biology. In the intervening years, a large number of studies have been carried out to investigate the toxicity of vanadium in higher animals and to determine whether it is an essential trace element. That vanadium is a required element for a few selected organisms is now well established. Whether vanadium is essential for humans remains unclear although evidence increasingly suggests that it probably is. The discovery by Cantley in 1977 that vanadate is a potent inhibitor of ATPases lead to numerous studies of the inhibitory and stimulatory effects of vanadium on phosphate metabolizing enzymes. As a consequence vanadates are now routinely used as probes to investigate the mechanisms of such enzymes. Our understanding of vanadium in these systems has been further enhanced by the work of Tracy and Gresser which has shown striking parallels between the chemistry of vanadates and phosphates and their biological compounds. The observation by Shechter and Karlish, and Dubyak and Kleinzeller in 1980 that vanadate is an insulin mimetic agent has opened a new area of research dealing with the hormonal effects of vanadium. The first vanadium containing enzyme, a bromoperoxidase from the marine alga Ascophyllum nodosum, was isolated in 1984 by Viltner.
Download or read book Encyclopedia of Biological Chemistry written by and published by Elsevier. This book was released on 2021-08-16 with total page 5350 pages. Available in PDF, EPUB and Kindle. Book excerpt: Encyclopedia of Biological Chemistry has always been characterized by its unique and comprehensive content. Since publication of the 2nd edition, many important discoveries have been made leading to novel concepts in several areas of biochemistry, and new technologies have advanced our understanding of key processes of life. All of these advances are included in the new and expanded third edition. This is the most up-to-date and complete resource on biochemistry and molecular biology, provided through contributions by leading experts in the field. A 'one-stop', comprehensive resource on "the chemistry of life", including a wealth of information and critical summaries to support research and teaching activities Each chapter is written concisely to guide the reader though the topic, using a consistent and unified terminology Clearly organized into seven logical sections, each curated by a world-leader in the field and the Editor in Chief
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.
