Characterizing the Domain- and Phosphorylation-requirements of the Interaction Between Peptidyl Prolyl Isomerase Pin1 and Mitotic Phosphatase CDC25C PDF Download
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Author: Dana Onica
Publisher:
ISBN:
Category :
Languages : en
Pages : 228
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Book Description
The enzyme Pin1 is a peptidyl-prolyl cis-trans isomerase consisting structurally of two domains, an N-terminal WW protein interaction domain and a C-terminal PPIase catalytic domain. Both domains bind a phosphorylated serine/threonine-proline motif, however, a precise mechanism regarding how binding to interactors is coordinated by both domains has not yet been determined. Although multiple models exist to explain this process, it appears that the interactions may be substrate-specific. With regards to a well-studied Pin1 interactor, CDC25C, we hypothesize that binding occurs via the simultaneous model. This model suggests that two binding sites, each having low affinity, may bind in concert producing a higher affinity interaction. To investigate this we chose to employ a peptide-based approach, using human CDC25C-derived peptides which contained the two identified Pin1 binding sites in phosphorylated and non-phosphorylated combinations. These peptides were utilized in two independent assays, surface plasmon resonance and fluorescence polarization, to elucidate the domain- and phosphorylation-requirements of the Pin1-CDC 25C interaction. We showed that the interaction is phosphorylation-dependent, and is optimal when full- length, wild-type Pin1 binds to a doubly-phosphorylated peptide. Collectively, our results support our hypothesis that the Pin1-CDC25C interaction occurs via the simultaneous model, and requires both domains.
Author: Dana Onica
Publisher:
ISBN:
Category :
Languages : en
Pages : 228
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Book Description
The enzyme Pin1 is a peptidyl-prolyl cis-trans isomerase consisting structurally of two domains, an N-terminal WW protein interaction domain and a C-terminal PPIase catalytic domain. Both domains bind a phosphorylated serine/threonine-proline motif, however, a precise mechanism regarding how binding to interactors is coordinated by both domains has not yet been determined. Although multiple models exist to explain this process, it appears that the interactions may be substrate-specific. With regards to a well-studied Pin1 interactor, CDC25C, we hypothesize that binding occurs via the simultaneous model. This model suggests that two binding sites, each having low affinity, may bind in concert producing a higher affinity interaction. To investigate this we chose to employ a peptide-based approach, using human CDC25C-derived peptides which contained the two identified Pin1 binding sites in phosphorylated and non-phosphorylated combinations. These peptides were utilized in two independent assays, surface plasmon resonance and fluorescence polarization, to elucidate the domain- and phosphorylation-requirements of the Pin1-CDC 25C interaction. We showed that the interaction is phosphorylation-dependent, and is optimal when full- length, wild-type Pin1 binds to a doubly-phosphorylated peptide. Collectively, our results support our hypothesis that the Pin1-CDC25C interaction occurs via the simultaneous model, and requires both domains.
Author: Michelle K. Dubinsky
Publisher:
ISBN:
Category :
Languages : en
Pages :
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Book Description
Pin1 is a human protein classified as a peptidyl-prolyl cis/trans isomerase. The protein regulates the conformation of phosphorylated protein substrates by rotating the peptide bond between phosphorylated serine/threonine residues that precede proline residues. Structurally, Pin1 consists of an N-terminal WW domain and a C-terminal PPIase domain. The PPIase domain catalyzes cis/trans isomerization of peptide bonds in substrate proteins that contain the aforementioned consensus motif. We hypothesize that Pin1 binding is positively impacted when two phospho-acceptor sites on peptides derived from mitotic phosphatase CDC25C, a known Pin1-interacting protein, are phosphorylated. Using nuclear magnetic resonance and fluorescence polarization, binding affinities of CDC25C peptides to Pin1 were calculated. The results indicate that doubly-phosphorylated peptides bound to Pin1 have lower dissociation constants and consequently greater binding affinities, than complexes containing non- or singly-phosphorylated peptides, at the equivalent residues. This suggests that Pin1 has two independent phospho-binding sites that when bound, increase substrate binding affinity.
Author: Moira M. Messenger
Publisher:
ISBN:
Category :
Languages : en
Pages : 206
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Author: Thomas E. Creighton
Publisher: Macmillan
ISBN: 9780716770305
Category : Medical
Languages : en
Pages : 534
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Book Description
Organized on a combined basis of chronology and of structural and functional hierarchy, This comprehensive text describes all aspects of proteins--biosynthesis, evolution, dynamics, ligand binding, catalysis, and energy transduction--not just their structures. This edition (first was 1984) is thoroughly updated--especially in the area of protein biosynthesis--and features end-of-chapter exercises and problems, many of which require the student to consult the cited literature in order to obtain the answer. Annotation copyright by Book News, Inc., Portland, OR
Author: Ralph A. Bradshaw
Publisher: Academic Press
ISBN: 0080533574
Category : Science
Languages : en
Pages : 2560
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Book Description
The Handbook of Cell Signaling 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 subject matter has been divided into five main parts (each of which is headed by a recognized expert in the field): * Initiation: Extracellular and Membrane Events * Transmission: Effectors and Cytosolic Events * Nuclear Responses: Gene Expression and Translation * Events in Intracellular Compartments * Cell-Cell and Cell-Matrix Interactions Covered in extensive detail, these areas will appeal to a broad, cross-disciplinary audience interested in the structure, biochemistry, molecular biology and pathology of cellular effectors. Tabular and well-illustrated, the Handbook will serve as an in-depth reference for this complex and evolving field. Tabular and well illustrated, the Handbook will serve as an in-depth reference for this complex and evolving field! * Contains approximately 470 articles * Provides well-organized sections on each essential area in signaling * Includes discussion on everything from ligand/receptor interactions to organ/organism responses * Extremely user-friendly
Author: Cai Huang
Publisher: BoD – Books on Demand
ISBN: 9535107372
Category : Medical
Languages : en
Pages : 482
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Book Description
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.
Author:
Publisher:
ISBN:
Category : Chemistry
Languages : en
Pages : 2676
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Author: Marc Thiriet
Publisher: Springer Science & Business Media
ISBN: 1461443695
Category : Science
Languages : en
Pages : 1073
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Book Description
The volumes in this authoritative series present a multidisciplinary approach to modeling and simulation of flows in the cardiovascular and ventilatory systems, especially multiscale modeling and coupled simulations. The cardiovascular and respiratory systems are tightly coupled, as their primary function is to supply oxygen to and remove carbon dioxide from the body's cells. Because physiological conduits have deformable and reactive walls, macroscopic flow behavior and prediction must be coupled to phenomenological models of nano- and microscopic events in a corrector scheme of regulated mechanisms when the vessel lumen caliber varies markedly. Therefore, investigation of flows of blood and air in physiological conduits requires an understanding of the biology, chemistry, and physics of these systems together with the mathematical tools to describe their functioning. Volume 4 is devoted to major sets of intracellular mediators that transmit signals upon stimulation of cell-surface receptors. Activation of signaling effectors triggers the release of substances stored in cellular organelles and/or gene transcription and protein synthesis. Complex stages of cell signaling can be studied using proper mathematical models, once the role of each component is carefully handled. Volume 4 also reviews various categories of cytosolic and/or nuclear mediators and illustrates some major signal transduction pathways, such as NFkappaB axis, oxygen sensing, and mechanotransduction.
Author: Nancy Y. Ip
Publisher: Springer Science & Business Media
ISBN: 0387788875
Category : Medical
Languages : en
Pages : 326
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Book Description
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.
Author: John F. Peberdy
Publisher: Springer Science & Business Media
ISBN: 1489919864
Category : Science
Languages : en
Pages : 305
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Book Description
Biotechnology is a word that was originally coined to describe the new processes which could be derived from our ability to manipulate, in vitro, the genetic material common to all organisms. I t has now become a generic term encompassing all "applications" of living systems, including the more traditional fermentation and agricultural industries. Recombinant DNA technology has opened up new opportunities for the exploitation of microorganisms and animal and plant cells as producers or modifiers of chemical and biological products. This series of handbooks deals exclusively with microorganisms which are at the forefront of the new technologies and brings together in each of its volumes the background information necessary to appreciate the historical development of the organisms making up a particular genus, the degree to which molecular biology has opened up new opportunities, and the place they occupy in today's biotechnology industry. Our aim was to make this primarily a practical approach, with emphasis on methodology, combining for the first time information which has largely been spread across a wide literature base or only touched upon briefly in review articles. Each handbook should provide the reader with a source text, from which the importance of the genus to his or her work can be identified, and a practical guide to the handling and exploitation of the organisms included.
