Scaffolding of the Cofilin Pathway by Beta-arrestin-1

Scaffolding of the Cofilin Pathway by Beta-arrestin-1 PDF Author: Alice Lin
Publisher:
ISBN:
Category : Arrestins
Languages : en
Pages : 0

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Scaffolding of the Cofilin Pathway by Beta-arrestin-1

Scaffolding of the Cofilin Pathway by Beta-arrestin-1 PDF Author: Alice Lin
Publisher:
ISBN:
Category : Arrestins
Languages : en
Pages : 0

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Molecular Mechanisms of Beta-Arrestin-1 Dependent Regulation of LIMK and Cofilin

Molecular Mechanisms of Beta-Arrestin-1 Dependent Regulation of LIMK and Cofilin PDF Author: Kyu Joon Lee
Publisher:
ISBN: 9781339729480
Category : Arrestins
Languages : en
Pages : 81

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Book Description
Beta-arrestins are adaptor proteins that can scaffold a number of signaling proteins to promote localized activity within the cell. Downstream of some GPCRs, [Beta]-arrestins can promote activation of the actin filament severing protein, cofilin, through two mechanisms: one involving inhibition of LIM Kinase (LIMK) which negatively regulates cofilin activity through phosphorylation on serine 3. The mechanism by which [Beta]-arrestin-1 regulates LIMK activity has not been elucidated; however, it has been shown to be important for cell migration downstream of protease-activate-receptor-2 (PAR-2), dendritic spine formation and opioid receptor function. Here my work demonstrate that [Beta]-arrestin-1 directly binds both cofilin and LIMK, and inhibits LIMK activity directly and investigate the mechanism by which inhibition of kinase activity occurs. Using serial truncations and site-directed mutagenesis, I identify crucial residues for cofilin and LIMK interaction within amino acids 1-99 of [Beta]-arrestin-1 and show that charged residues at 50 and 51 are crucial for binding to LIMK and R51 is required for LIMK inhibition, PAR2 stimulated cofilin dephosphorylation and cell migration. Additionally, our work reveals that amino acids 1-99 aminos of [Beta]-arrestin-1 bind both cofilin and LIMK with a higher apparent affinity than the full length and blocks PAR2-stimulated cofilin dephosphorylaton in HEK293 cells, suggesting it functions as a selective dominant negative [Beta]-arrestin-1, inhibiting specifically the cofilin pathway. Thus, residues in the N-terminus of [Beta]-arrestin-1 are involved in LIMK inhibition and cofilin activation and this, in turn, is important for cell migration downstream of PAR-2.

The Structural Basis of Arrestin Functions

The Structural Basis of Arrestin Functions PDF Author: Vsevolod V. Gurevich
Publisher: Springer
ISBN: 3319575538
Category : Science
Languages : en
Pages : 302

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Book Description
This volume summarizes our current understanding of the structural basis of the functions of arrestin family of proteins. Arrestins were first discovered as key players in the desensitization of G protein-coupled receptors (GPCRs). Recent studies showed that arrestins are important signal transducers in their own right, organizing multi-protein complexes and scaffolding numerous signaling cascades that regulate cell proliferation, differentiation, and apoptotic death. Here arrestin functions are described primarily from the structural prospective. The book covers basal structure of arrestin proteins, receptor binding-induced conformational changes in arrestins, as well as the structure of “pre-activated” mutants. Particular focus is on the arrestin elements interacting with numerous binding partners, GPCRs and cytoplasmic signaling proteins. We expect that this information and insights will help to understand and exploit the phenomenon of signaling bias, which is a new promising direction in drug discovery. The chapters are written by the world-class specialists in the field, mostly the people who actually contributed the data discussed. The book gives coherent historical prospective and describes the most recent findings. The book would be particularly useful for scientists in academia and industry working in the fields of pharmacology, cell biology, structural biology, and drug discovery. We expect that the focus on the molecular basis of protein-protein interactions would help to develop novel tools for engaging this important type of targets for research and therapeutic purposes.

Arrestins - Pharmacology and Therapeutic Potential

Arrestins - Pharmacology and Therapeutic Potential PDF Author: Vsevolod V. Gurevich
Publisher: Springer Science & Business Media
ISBN: 3642411991
Category : Medical
Languages : en
Pages : 441

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Book Description
This volume describes our current understanding of the biological role of visual and non-visual arrestins in different cells and tissues, focusing on the mechanisms of arrestin-mediated regulation of GPCRs and non-receptor signaling proteins in health and disease. The book covers wide range of arrestin functions, emphasizing therapeutic potential of targeting arrestin interactions with individual partners.

Proteases and Their Receptors in Inflammation

Proteases and Their Receptors in Inflammation PDF Author: Nathalie Vergnolle
Publisher: Springer Science & Business Media
ISBN: 3034801572
Category : Medical
Languages : en
Pages : 318

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Book Description
Proteases are everywhere from prokaryotes to eukaryotes, from virus to bacteria and in all human tissues, playing a role in many biological functions. Among these functions, the inflammatory reaction is of particular interest. In inflamed tissues, proteases can have a microbial and/or host origin and are involved not only in tissue remodeling, but also in specific signaling to resident or inflammatory cells, thereby contributing to the innate immune response. This volume presents all advances in our knowledge of the role proteases and their inhibitors play in various diseases associated with inflammatory response. Mechanisms involved in protease signaling to cells are presented, and the different types of proteases that are present at inflammatory sites and their effects on the course of inflammation are discussed. Finally, the evidence for considering proteases and their receptors as potential molecular targets for therapeutic interventions in the treatment of inflammatory diseases is discussed in the context of specific organ inflammatory pathologies (the lung, gastrointestinal tract, skin, joints, etc.).

The Molecular Biology of Arrestins

The Molecular Biology of Arrestins PDF Author:
Publisher: Academic Press
ISBN: 0123947898
Category : Science
Languages : en
Pages : 545

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Book Description
This special volume of Progress in Molecular Biology and Translational Science focuses on the molecular biology of arrestins, with contributions from leaders in the field. Arrestins have emerged as central players in the regulation of many facets of G protein-coupled receptor signaling. This volume covers a variety of topics with reviews written by experts in the field. - Contributions from leading authorities - Informs and updates on all the latest developments in the field

G Protein-Coupled Receptor Kinases (GRKs) and Beta-Arrestins: New Insights into Disease Regulators

G Protein-Coupled Receptor Kinases (GRKs) and Beta-Arrestins: New Insights into Disease Regulators PDF Author: Yuichi Hattori
Publisher: Frontiers Media SA
ISBN: 2889635473
Category :
Languages : en
Pages : 182

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Book Description


Hemostasis and Thrombosis

Hemostasis and Thrombosis PDF Author: Victor J. Marder
Publisher: Lippincott Williams & Wilkins
ISBN: 1451177690
Category : Medical
Languages : en
Pages : 5220

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Book Description
Since publication of the First Edition in 1982, Hemostasis and Thrombosis has established itself as the pre-eminent book in the field of coagulation disorders. No other book is as inclusive in scope, with coverage of the field from the standpoint of both basic scientists and clinicians. This comprehensive resource details the essentials of bleeding and thrombotic disorders and the management of patients with these and related problems, and delivers the most up-to-date information on normal biochemistry and function of platelets or endothelial cells, as well as in-depth discussions of the pharmacology of anticoagulant, fibrinolytic, and hemostatic drugs. NEW to the Sixth Edition... • A new team of editors, each a leader in his field, assures you of fresh, authoritative perspectives. • Full color throughout • A companion website that offers full text online and an image bank. • A new introductory section of chapters on basic sciences as related to the field • Entirely new section on Hemostatic and Thrombotic Disorders Associated with Systemic Conditions includes material on pediatric patients, women's health issues, cancer, sickle cell disease, and other groups. • Overview chapters preceding each section address broad topics of general importance. This is the tablet version which does not include access to the supplemental content mentioned in the text.

Guide to Signal Pathways in Immune Cells

Guide to Signal Pathways in Immune Cells PDF Author: E. Nigel Wardle
Publisher: Springer Science & Business Media
ISBN: 160327538X
Category : Medical
Languages : en
Pages : 425

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Book Description
To read current biomedical science, one has to have a working knowledge of how important effector molecules cause transduction of their signal within cells, altering the control of genes. This work aims to provide that basic knowledge for medical readers. Students of immunology or cell biology will note its relevance. One will learn how platelets, macrophages, neutrophils, T and B lymphocytes and natural killer cells perform their functions and how skin, breast, prostate and colon cancers emerge. The associated diagrams and tables are used to obviate extensive text. Appropriate references to articles and reviews by workers in each field are given so that further consideration can easily be undertaken. We are all at differing stages of our appreciation of immunology and of pat- physiology. Some persons will have a profound background in biochemistry or molecular biology. Others will have a reminiscence of lectures received years ago. Since this work is principally for clinical doctors, the sections that can be avoided at first reading are marked with an asterisk (*). Always proceed line by line and think of associations that you know. Do you feel comfortable with the statement, “Interleukin 6 stimulates glucose uptake in renal proximal tubular cells, and that action is associated with Stat3, PI3K/Akt, MAPKs and NF-kB signal pathways”? If not, please read on.

Neuropeptide Receptors

Neuropeptide Receptors PDF Author: Ivone Gomes
Publisher: Biota Publishing
ISBN: 1615044698
Category : Medical
Languages : en
Pages : 169

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Book Description
Neuropeptides mediate their effects by binding and activating receptors that are responsible for converting these extracellular stimuli into intracellular responses. Most neuropeptides interact with G protein-coupled receptors that transduce the signal by activating heterotrimeric G proteins leading to alterations in second messenger systems to amplify the signal and elicit the intracellular response. In this review, we describe the general structure of G protein-coupled receptors including the information obtained from crystal structure determination that has given an insight into the activation mechanism of these receptors. In addition, we summarize the components of the signal transduction system (including G proteins, effectors and second messengers generally activated by the neuropeptide receptors). Using select examples of neuropeptide-receptor systems, we highlight the neuropeptides and corresponding receptors involved in modulation of pain and analgesia, body weight regulation, and hormonal regulation. Finally, we discuss the enzyme-linked tyrosine kinase receptors activated by growth factors and discuss the emerging concepts in targeting neuropeptide receptors for the identification of novel therapeutics targeting these systems. Table of Contents: Abbreviations / Overview of Neuropeptide Receptors / G Protein-Coupled Receptors: General Structure & Function / G Protein-Coupled Receptor Signaling / Neuropeptide Processing and Regulation / Neuropeptide Receptors / Perspectives / References