Download or read book Regulation of the Structure and Function of Protein Kinase C written by Jeffrey Wallace Orr and published by . This book was released on 1994 with total page 254 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Protein Kinase C Protocols written by Alexandra C. Newton and published by Springer Science & Business Media. This book was released on 2008-02-03 with total page 565 pages. Available in PDF, EPUB and Kindle. Book excerpt: Since the discovery that protein kinase C (PKC) transduces the ab- dance of signals that result in phospholipid hydrolysis, this enzyme has been at the forefront of research in signal transduction. Protein Kinase C Protocols covers fundamental methods for studying the structure, function, regulation, subcellular localization, and macromolecular interactions of PKC. Protein Kinase C Protocols is divided into 11 sections representing the major aspects of PKC regulation and function. Part I contains an introduction and a historical perspective on the discovery of PKC by Drs. Yasutomi Nishizuka and Ushio Kikkawa. Part II describes methods to purify PKC. Part III describes the standard methods for measuring PKC activity: its enzymatic activity and its stimulus-dependent translocation from the cytosol to the membrane. Part IV describes methods for measuring the membrane interaction of PKC in vivo and in vitro. Part V provides methodologies and techniques for measuring the ph- phorylation state of PKC, including a protocol for measuring the activity of PKC’s upstream kinase, PDK-1. Novel methods for identifying substrates are described in Part VI. Part VII presents protocols for expressing and analyzing the membrane targeting domains of PKC. Part VIII provides a comprehensive c- pilation of methods used to identify binding partners for PKC. Part IX describes pharmacological probes used to study PKC. The book ends with a presentation of genetic approaches to study PKC (Part X) and a discussion of approaches used to study PKC in disease (Part XI).

Download or read book Protein Kinase C written by Lodewijk V. Dekker and published by Springer Science & Business Media. This book was released on 2004-06-17 with total page 212 pages. Available in PDF, EPUB and Kindle. Book excerpt: Protein Kinase C is a pivotal component of the mechanism that allows a cell to respond to its changing environment. In this book, the most significant advances in recent basic research on Protein Kinase C are explained by active researchers in the field. The first seven chapters provide a comprehensive account of the fundamental structural and biochemical properties of Protein Kinase C. The remaining chapters contain overviews of the function of Protein Kinase C, both in lower organisms and in mammalian cells, the latter with a focus on immune cells and nerve cells. This book is the only recent publication devoted entirely to Protein Kinase C and forms a major point of reference for those active in the field. In addition it will appeal to those with a general interest in biochemistry, cell biology, immunology and neurobiology.

Download or read book Protein Kinase C written by and published by . This book was released on 1994 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Protein Kinase mediated Decisions Between Life and Death written by Ayse Basak Engin and published by Springer Nature. This book was released on 2021-02-04 with total page 415 pages. Available in PDF, EPUB and Kindle. Book excerpt: Protein phosphorylation via protein kinases is an inevitable process that alters physiological and pathological functions of the cells. Thus, protein kinases play key roles in the regulation of cell life or death decisions. Protein kinases are frequently a driving factor in a variety of human diseases including aging and cellular senescence, immune system and endothelial dysfunctions, cancers, insulin resistance, cholestasis and neurodegenerative diseases, as well as bacterial resistance in persistent infections. Recent developments in quantitative proteomics provide important opinions on kinase inhibitor selectivity and their modes of action in the biological context. Protein Kinase-mediated Decisions Between Life and Death aims to have the reader catch insights about up-to-date opinions on “Protein Kinases” related pathways that threaten human health and life. As “Protein Kinases” are related to many health problems, clinicians, basic science researchers and students need this information. Chapter “Signal Transduction in Immune Cells and Protein Kinases” is available open access under a Creative Commons Attribution 4.0 International License via link.springer.com.

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 Interferon The 50th Anniversary written by Paula M. Pitha and published by Springer Science & Business Media. This book was released on 2007-08-29 with total page 385 pages. Available in PDF, EPUB and Kindle. Book excerpt: A vital text for researchers and clinicians in the fields of virology and oncology alike, this book is a comprehensive guide to one of medicine’s most important tools that covers the most recent research. Important insights have been made in recent months that are challenging the accepted concept of the critical role of dsRNA in IFN induction. Recent work with genetically modified mice seems to confirm the original idea that interferon is the first cellular defense against viral infection.

Download or read book Structural Features of Protein Kinase C Regulate Its Downregulation and Phosphatase Sensitivity written by Alexander Curtis Jones and published by . This book was released on 2023 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Post-translational modifications govern almost every aspect of cell biology. The addition and removal of functional groups on proteins lead to complex signal transduction pathways. This dissertation focuses on elucidating regulatory mechanisms of two enzymes whose activity and signaling are interlocked in the serine/threonine phosphorylation realm: Protein Kinase C (PKC) and Protein Phosphatase 2A (PP2A). The conventional class of PKC isozymes (cPKC) is transiently activated by Ca2+ and diacylglycerol (DG) to allow phosphorylation of downstream substrates. Importantly, in the absence of these second messengers, PKC adopts an autoinhibited conformation where it has low activity and is quite stable in the cell. We first address the need for a structure of autoinhibited PKC by building a model of this conformation to generate testable hypotheses as to important residues that are involved in interdomain contacts. The second part of this dissertation utilizes our model to assess the effect of two disease-associated mutations at the same position (R42H from cancer and R42P from spinocerebellar ataxia) that are both predicted to disrupt an interaction that contributes to autoinhibition. Mutations that disrupt autoinhibitory contacts typically result in quality-control degradation. We use biochemical, cellular, and structural approaches to demonstrate that these mutants have higher basal activity and are in an open conformation as our model predicts. Whereas histidine at this position allows canonical downregulation both basally and in response to activators, R42P bypasses the ubiquitination associated with activator-induced degradation. These studies highlight the fine-tuning of PKC levels in the cell and provide examples of how two diseases manipulate this regulation to exert opposing effects on PKC. Finally, we examined potential mechanisms by which PP2A regulates PKC dephosphorylation and levels. We show that a novel motif identified on PKC may contribute to its rate of dephosphorylation and that the PP2A regulatory subunit B56[delta] can regulate PKC expression through regions of B56[delta] that are not conserved within the B56 family. Together, this work illustrates multiple mechanisms of PKC regulation with the goal of understanding how to properly target PKC isozymes in disease.

Download or read book Biology of the NMDA Receptor written by Antonius M. VanDongen and published by CRC Press. This book was released on 2008-10-29 with total page 368 pages. Available in PDF, EPUB and Kindle. Book excerpt: The NMDA receptor plays a critical role in the development of the central nervous system and in adult neuroplasticity, learning, and memory. Therefore, it is not surprising that this receptor has been widely studied. However, despite the importance of rhythms for the sustenance of life, this aspect of NMDAR function remains poorly studied. Written

Download or read book Protein Kinases and Stress Signaling in Plants written by Girdhar K. Pandey and published by John Wiley & Sons. This book was released on 2020-12-03 with total page 560 pages. Available in PDF, EPUB and Kindle. Book excerpt: A comprehensive review of stress signaling in plants using genomics and functional genomic approaches Improving agricultural production and meeting the needs of a rapidly growing global population requires crop systems capable of overcoming environmental stresses. Understanding the role of different signaling components in plant stress regulation is vital to developing crops which can withstand abiotic and biotic stresses without loss of crop yield and productivity. Emphasizing genomics and functional genomic approaches, Protein Kinases and Stress Signaling in Plants is a comprehensive review of cutting-edge research on stress perception, signal transduction, and stress response generation. Detailed chapters cover a broad range of topics central to improving agricultural production developing crop systems capable of overcoming environmental stresses to meet the needs of a rapidly growing global population. This book describes the field of protein kinases and stress signaling with a special emphasis on functional genomics. It presents a highly valuable contribution in the field of stress perception, signal transduction and generation of responses against one or multiple stress signals. This timely resource: Summarizes the role of various kinases involved in stress management Enumerates the role of TOR, GSK3-like kinase, SnRK kinases in different physiological conditions Examines mitogen-activated protein kinases (MAPKs) in different stresses Describes the different aspects of calcium signaling under different stress conditions Examines photo-activated kinases (PAPKs) in varying light conditions Briefs the presence of tyrosine kinases in plants Highlights the cellular functions of receptor ]like protein kinases (RLKs) Possible implication of these kinases in developing stress tolerant crops Protein Kinases and Stress Signaling in Plants: Functional Genomic Perspective is an essential resource for researchers and students in the fields of plant molecular biology and signal transduction, plant responses to stress, plant cell signaling, plant protein kinases, plant biotechnology, transgenic plants and stress biology.

Download or read book Protein Kinase CK2 From Structure to Regulation written by Khalil Ahmed and published by Springer Science & Business Media. This book was released on 2012-12-06 with total page 180 pages. Available in PDF, EPUB and Kindle. Book excerpt: CK2 is a protein serine/threonine kinase which is a highly conserved and ubiquitous protein kinase. It is localized in the cytoplasmic and nuclear compartments, which accords with its multiple functional activities in the cell. Pertinent to this is also the recognition that a large number of putative substrates for this kinase have been identified in various compartments of the cell. New evidence from several laboratories has further reinforced the involvement of CK2 in signal transduction related to many cellular functions, thus underscoring the significance of its functional role in normal and abnormal cell growth and proliferation. This volume provides an overview of the state of knowledge concerning this intriguing protein kinase. It brings together contributions from leading investigators engaged in research in this field. Key developments during the past three years pertain to the elaboration of the crystal structure and definition of novel functions of the kinase, such as its role as an inhibitor of apoptosis. Additionally, the shuttling of the kinase to various compartments in response to physiological and stress stimuli appears to be a key feature of the functional regulation of its activity in the cell.

Download or read book Cyclin Dependent Kinase 5 Cdk5 written by Nancy Y. Ip and published by Springer Science & Business Media. This book was released on 2009-02-28 with total page 326 pages. Available in PDF, EPUB and Kindle. Book excerpt: Cyclin Dependent Kinase 5 provides a comprehensive and up-to-date collection of reviews on the discovery, signaling mechanisms and functions of Cdk5, as well as the potential implication of Cdk5 in the treatment of neurodegenerative diseases. Since the identification of this unique member of the Cdk family, Cdk5 has emerged as one of the most important signal transduction mediators in the development, maintenance and fine-tuning of neuronal functions and networking. Further studies have revealed that Cdk5 is also associated with the regulation of neuronal survival during both developmental stages and in neurodegenerative diseases. These observations indicate that precise control of Cdk5 is essential for the regulation of neuronal survival. The pivotal role Cdk5 appears to play in both the regulation of neuronal survival and synaptic functions thus raises the interesting possibility that Cdk5 inhibitors may serve as therapeutic treatment for a number of neurodegenerative diseases.

Download or read book Protein Phosphorylation in Cell Growth Regulation written by Michael J. Clemens and published by CRC Press. This book was released on 1996-12-03 with total page 300 pages. Available in PDF, EPUB and Kindle. Book excerpt: The aim of this text is to integrate the processes of protein phosphorylation and dephosphorylation into the complex pathways by which cellular proliferation is driven, bringing together the many different systems of control implicated in the regulation of cell growth. Presents a survey of protein phosphorylation roles in the control of cellular proliferation and differentiation. A large number of protein kinases and phosphatases have been characterised in higher cells, and have been shown to be involved in signal transduction pathways by which growth factors, mitogens, and extracellular agents exert proliferative effects on cells. Important subjects covered include control of gene expression at the transcriptional and translational levels, and roles of the cdk kinases and cyclins in cell cycles regulation. Describes all major families of protein kinases of significance to growth regulation.

Download or read book Protein Kinase C in Cancer Signaling and Therapy written by Marcelo G. Kazanietz and published by Springer Science & Business Media. This book was released on 2010-06-10 with total page 492 pages. Available in PDF, EPUB and Kindle. Book excerpt: Protein kinase C (PKC), a family of serine-threonine kinases, rocketed to the forefront of the cancer research field in the early 1980’s with its identification as an effector of phorbol esters, natural products with tumor promoting activity. Phorbol esters had long been of interest to the cancer research field due to early studies in the mouse skin carcinogenesis model, which showed that prolonged topical application of phorbol esters promoted the formation of skin tumors on mice previously treated with mutagenic agents. Research in the last years has established key roles for PKC isozymes in the control of cell proliferation, migration, adhesion, and malignant transformation. In addition, there is a large body of evidence linking PKC to invasion and cancer cell metastasis. Moreover, it is now well established that the expression of PKC isozymes is altered in various types of cancers. More importantly, small molecule inhibitors have been developed with significant anti-cancer activity. The relevance of PKC isozymes in cancer signaling is therefore remarkable. This book will have 4 sections. There will be 23 chapters. Each section will have a brief introduction by an expert in the field (~ 1-2 pages).

Download or read book Smad Signal Transduction written by Peter Dijke and published by Springer Science & Business Media. This book was released on 2007-05-10 with total page 489 pages. Available in PDF, EPUB and Kindle. Book excerpt: This is the first comprehensive book on Smad signal transduction. Forward looking reviews of Smads are provided in a series of 22 cutting-edge chapters. The book is written for an audience with basic understanding of molecular and cell biology. This volume provides an in-depth review of a rapidly developing field and extensive cross-references between chapters are provided.

Download or read book Mechanisms of Stimulus induced Protein Kinase C Regulation written by Michelle Lum and published by . This book was released on 2012 with total page 188 pages. Available in PDF, EPUB and Kindle. Book excerpt: Protein Kinase C (PKC) is a family of AGC kinases (a family including the A, G, and C protein kinases) that play critical roles in regulation of cell growth and cell cycle progression, differentiation, cell survival and apoptosis, gene expression, receptor trafficking and desensitization, and cell transformation. As regulators of fundamental cellular processes, the activity of members of this family is tightly controlled. While mechanisms of activation of these proteins have been extensively characterized, the pathways underlying signal termination are less well understood. PKCs are divided into 3 classes based on structure and coactivator requirements. Classical PKC (cPKC: PKC alpha, PKC beta I, PKC beta II and PKC gamma) are activated by diacylglycerol (DAG), Ca2+ and phosphatidylserine, while novel PKC (nPKC) do not require Ca2+ and atypical PKC (aPKC) are independent of both DAG and Ca2+.^The difference in cofactor requirements for these isozymes is a result of differences in their C1 and C2 regulatory domain structures. The C1 domain is involved in DAG binding, while the C2 domain is involved in Ca2+ binding. Ligand binding by a number of growth factor and cytokine receptors leads to activation of phospholipase C and subsequent generation of DAG and inositide trisphosphate (which mobilizes intracellular Ca2+). The accumulation of DAG leads to recruitment of cPKCs and nPKCs to the plasma membrane where they are activated due to displacement of a pseudosubstrate domain from the active site. In addition to activation by physiological signals, cPKCs and nPKCs can also be activated by pharmacological agonists that bind to the same site as DAG. These agonists include phorbol esters, such as phorbol 12-myristate 13-acetate (PMA), and bryostatins, such as bryostatin-1 (bryo). Newly synthesized PKCs are not competent for activation but require priming phosphorylation on three conserved sites on the activation loop, turn motif and hydrophobic motif. These priming phosphorylations, which occur in an ordered manner, render the kinase competent for activation and stabilize it against denaturation and degradation. Acute termination of signaling is achieved by the rapid metabolism of DAG (by e. g., diacylglycerol kinase). This loss of signal leads to "reverse translocation" of membrane bound PKC to the cytoplasm in a process that is dependent on kinase activity. Pharmacological agonists are not subject to rapid metabolism and thus elicit a sustained activation of PKCs. In addition to acute termination of signal, it has long been recognized that prolonged activation of PKCs (either by pharmacological agonists or sustained physiological stimuli) leads to desensitization of this signaling system via degradation of the protein. Although activation-induced loss of PKC expression has been observed in many systems, there is considerable confusion regarding the mechanism(s) underlying agonist-induced desensitization of PKC signaling. Part of this confusion may stem from the extensive use of overexpression systems to analyze aspects of PKC regulation. While these systems can yield valuable information, our analysis indicates that overexpression can drive activated PKC isozymes into alternate pathways of degradation, which do not reflect those utilized by the endogenous proteins. Studies detailed herein analyze various mechanisms of desensitization of PKC signaling that are relevant to the endogenous protein by examining the effects of various agonists on the localization and processing of cellular PKC alpha.^The first part of this work used a combination of biochemical and immunolocalization studies to examine the mechanisms underlying a novel non-proteasomal pathway of degradation that is induced by prolonged bryo treatment in various cell types. Bryo initially induces translocation of endogenous PKC alpha; to the plasma membrane, where a pool of the protein is subjected to proteasomal degradation. A second subpopulation is internalized through a clathrin-independent, but cholesterol- and genistein-sensitive pathway, which involves trafficking through EEA1-positive early endosomes and Rab7-positive late endosomes/multivesicular bodies. The ultimate fate of internalized PKC alpha is degradation by lysosomal proteases in the perinuclear region. Analysis of the effect of endolysosomal disrupting agents in multiple cell lines points to lysosomal processing of activated PKC alpha as a common mechanism for its desensitization. The second part of this thesis explored the role of dephosphorylation and heat shock proteins (Hsps) in agonist-induced proteasomal degradation of endogenous PKC alpha. A widely accepted mechanism for stimulus-induced downregulation of PKCs involves priming site dephosphorylation, which targets the protein for proteasomal degradation. However, studies described here demonstrate that PKC agonists induce downregulation of endogenous PKCalpha with minimal accumulation of non-phosphorylated enzyme in multiple cell types. Furthermore, all or most of the non-phosphorylated enzyme detected in agonist-treated cells results from delayed maturation rather than dephosphorylation of the protein. Thus, PKC agonists induce at most low levels of dephosphorylation of endogenous PKC alpha;, and dephosphorylation is not a prerequisite for enzyme degradation. Analysis of the functions of Hsp90 and Hsp70/Hsc70 revealed distinct roles for these chaperones in regulating agonist-induced PKC alpha; degradation. Hsp90 prevents dephosphorylation of the activated enzyme and protects the mature, phosphorylated form of protein from proteasomal clearance following activation. In contrast, while Hsp70/Hsc70 also protects PKC alpha; from dephosphorylation, it enhances degradation of activated PKC alpha; by facilitating proteasomal processing of mature phosphorylated protein. Notably, downregulation of non-phosphorylated enzyme showed little dependence on Hsp70/Hsc70, suggesting that mature and non-phosphorylated species are targeted for proteasomal degradation via different pathways. Finally, lysosomal degradation of PKC alpha is not dependent on Hsps or the phosphorylation state of the enzyme. The third part of this work examines desensitization of PKC signaling following stimulation by DAG, the major physiological activator of cPKC and nPKC isozymes.^Analysis of the effects of a single addition of various DAGs (which are rapidly metabolized), and of short term pulse treatment with phorbol esters, confirmed that acute reversal of PKC alpha signaling following loss of signal involves dissociation of fully phosphorylated PKC alpha from the plasma membrane and cytosolic accumulation of the enzyme, via a mechanism that is dependent on PKC alpha activity. In contrast, repeated addition of DAGs resulted in sustained association of PKC alpha with the plasma membrane, in a pattern comparable with that induced by the phorbol ester PMA. Unlike the effects of PMA, however, chronic DAG stimulation failed to promote degradation/downregulation of PKC alpha, although downregulation of PKC delta and epsilon was readily apparent. Priming site dephosphorylation of PKC alpha was also not observed and Hsp70/Hsc70 and Hsp90 were excluded as regulators of PKC alpha phosphorylation and stability in this context. Importantly, while long-term activation of PKC alpha by DAG did not lead to degradation of the enzyme, it did induce desensitization of PKC alpha signaling, as seen by reversal of PKC alpha mediated effects on ERK activation, p21Waf1/Cip1 induction, and Id1 and cyclin D1 downregulation. These findings point to a previously undefined mechanisms for desensitization of PKC alpha, which can be attributed either to direct effects on PKC alpha function or to alterations in its downstream signaling pathways. Through analysis of the endogenous protein, each of these studies has identified a novel mechanism for desensitization of PKC alpha signaling. Collectively, the data confirm that the phosphorylated species of PKC alpha is a direct target for proteasomal and lysosomal degradation, and highlight the existence of multiple mechanisms for processing activated PKCs in cells.

Download or read book Receptor Tyrosine Kinases Structure Functions and Role in Human Disease written by Deric L. Wheeler and published by Springer. This book was released on 2014-11-26 with total page 452 pages. Available in PDF, EPUB and Kindle. Book excerpt: Receptor Tyrosine Kinase: Structure, Functions and Role in Human Disease, for the first time, systematically covers the shared structural and functional features of the RTK family. Receptor Tyrosine Kinases (RTKs) play critical roles in embryogenesis, normal physiology and several diseases. And over the last decade they have become the Number 1 targets of cancer drugs. To be able to conduct fundamental research or to attempt to develop pharmacological agents able to enhance or intercept them, it is essential first to understand the evolutionary origin of the 58 RTKs and their roles in invertebrates and in humans, as well as downstream signaling pathways. The assembly of chapters is written by experts and underscores commonalities between and among the RTKs. It is an ideal companion volume to The Receptor Tyrosine Kinase: Families and Subfamilies, which proceeds, family by family through all of the specific subfamilies of RTKs, along with their unique landmarks.