Sonnets: Three Volume Gift Set

《Sonnets: Three Volume Gift Set》是Pushkin Press; Gift edition出版的圖書，作者是威廉·莎士比亞。

基本介紹

• 中文名：Sonnets: Three Volume Gift Set
• 作者：威廉•莎士比亞 (William Shakespeare)
• 出版社：Pushkin Press; Gift edition
• 頁數：486 頁
• 定價：37.23 美元 
• 裝幀：精裝
• ISBN：9781906548001 

作者簡介

William Shakespeare lived between 1552-1616, but his work endures and is enjoyed the world over. --This text refers to the Audio Cassette edition.

內容簡介

Shakespeare's sonnets are thought to have been written for a private audience across several years, before being published in 1609. The verses that compose the sonnets are often subversive, elusive, and intimate, shaping an erotic body of poetry in the pursuit of the depths and parameters of emotion. He seems to have planned contrasting series--bitter sequences of lust and recrimination haunted by a married "dark lady," lyrics praising youth and beauty addressed to a "fair youth," and allegorical contemplations of Greek myth.

Shakespeare's sonnets are thought to have been written for a private audience across several years, before being published in 1609.

媒體評論

Shakespeare's sonnets are thought to have been written for a private audience across several years, before being published in 1609. The verses that compose the sonnets are often subversive, elusive, and intimate, shaping an erotic body of poetry in the pursuit of the depths and parameters of emotion. He seems to have planned contrasting series--bitter sequences of lust and recrimination haunted by a married "dark lady," lyrics praising youth and beauty addressed to a "fair youth," and allegorical contemplations of Greek myth.

主要內容

Cover image

Title page

Table of Contents

Copyright

Contributors

Preface

VOLUME 1

Chapter 1: Cell Signaling: Yesterday, Today, and Tomorrow

Origins of Cell Signaling

Enter Polypeptide Growth Factors

Cell Signaling at the Molecular Level

Lipid Signaling

Cell Signaling Tomorrow

PART I: INITIATION: EXTRACELLULAR AND MEMBRANE EVENTS

Introduction

Section A: Molecular Recognition

Chapter 2: Structural and Energetic Basis of Molecular Recognition

Introduction

Principles of Binding

Nonspecific Association with Membrane Surfaces

Protein–Protein Interactions

Prospects

Chapter 3: Computational Genomics: Prediction of Protein Functional Linkages and Networks

Introduction

Approaches to Analyzing Protein Functions on a Genome-Wide Scale

Current Issues and Future Prospects for Computing Functional Interactions

Acknowledgments

Chapter 4: Molecular Sociology

Transmembrane Signaling Paradigms

Structural Basis of Protein–Protein Recognition

Conclusion

Chapter 5: Free Energy Landscapes in Protein–Protein Interactions

Introduction

Thermodynamics of Protein–Protein Interactions

Interaction Kinetics

The Transition State

Association of a Protein Complex

Dissociation of a Protein Complex

Summary

Chapter 6: Antibody–Antigen Recognition and Conformational Changes

Introduction

Antibody Architecture

Conformational Changes

Conclusion

Acknowledgments

Chapter 7: Binding Energetics in Antigen–Antibody Interfaces

Introduction

Thermodynamic Mapping of Antigen–Antibody Interfaces

Conclusions

Chapter 8: Immunoglobulin–Fc Receptor Interactions

Introduction

IgG–Receptor Interactions

IgE–Receptor Interactions

Summary

Chapter 9: Plasticity of Fc Recognition

Introduction

Structures of the Natural Fc Binding Domains

The Consensus Binding Site on Fc

Evolution of an Fc Binding Peptide

Factors Promoting Plasticity

Conserved and Functionally Important Molecular Interactions

Conclusion

Chapter 10: Ig-Superfold and Its Variable Uses in Molecular Recognition

Introduction

The Immunoglobulin Superfamily

Ig-Superfold-Mediated Recognition

Chapter 11: T-Cell Receptor/pMHC Complexes

TCR Generation and Architecture

Peptide Binding to MHC Class I and II

TCR/pMHC Interaction

Conclusions and Future Perspectives

Acknowledgments

Chapter 12: Mechanistic Features of Cell-Surface Adhesion Receptors

Mechanosensory Mechanisms

Cell–Cell Adhesions/Adherens Junctions

T-Cell Costimulation

Axon Guidance and Neural Development

Conclusions

Chapter 13: The Immunological Synapse

Introduction

Migration and the Immunological Synapse

The Cytoskeleton and the Immunological Synapse

The Role of Self MHCp in T-Cell Sensitivity to Foreign MHCp

Integration of Adaptive and Innate Responses

Summary

Acknowledgments

Chapter 14: NK Receptors

Introduction

Immunoreceptors

Natural Killer Cells

Ig-Type NK Receptors: KIR

C-Type Lectin-Like NK Receptors: Ly49A

C-Type Lectin-Like NK Receptors: NKG2D

Chapter 15: Carbohydrate Recognition and Signaling

Introduction

Biological Roles of Carbohydrate Recognition

Carbohydrate Structure and Diversity

Lectins and Carbohydrate Recognition

Carbohydrate-Mediated Signaling

Conclusions

Chapter 16: Rhinovirus–Receptor Interactions

Chapter 17: HIV-1 Receptor Interactions

Molecular Interactions

Atomic Details

Recognition in the Context of a Humoral Immune Response

Chapter 18: Influenza Virus Neuraminidase Inhibitors

Introduction

Flu Virus: Role of NA

Structure of NA

Active Site

Inhibitor Development

Conclusion

Acknowledgments

Chapter 19: Signal Transduction and Integral Membrane Proteins

Introduction

Electrophysiology: Rapid Signal Transduction

Mechanosensation: How Do We Feel?

Active Transporters: Rapid Response and Energy Management

Receptors: Gate Keepers for Cell Signaling

Chapter 20: Structural Basis of Signaling Events Involving Fibrinogen and Fibrin

Chapter 21: Structural Basis of Integrin Signaling

Introduction

Structure

Quaternary Changes

Tertiary Changes

Tail Interactions

Concluding Remarks

Chapter 22: Structures of Heterotrimeric G Proteins and Their Complexes

Introduction

Gα Subunits

Ga–Effector Interactions

GTP Hydrolysis by Gα and Its Regulation by RGS Proteins

Gβγ Dimers

GPR/GoLoco Motifs

Gα–GPCR Interactions

Section B: Vertical Receptors

Chapter 23: Structure and Function of G-Protein-Coupled Receptors: Lessons from the Crystal Structure of Rhodopsin

Introduction

Introduction to Rhodopsin: a Prototypical G-Protein-Coupled Receptor

Molecular Structure of Rhodopsin

Molecular Mechanism of Receptor Activation

Chapter 24: Human Olfactory Receptors

Chapter 25: Chemokines and Chemokine Receptors: Structure and Function

Introduction

Chemokine Structure and Function

Chemokine Receptors

Chapter 26: The Binding Pocket of G-Protein-Coupled Receptors for Biogenic Amines, Retinal, and Other Ligands

Introduction

The Binding Pocket of GPCRs

A Role of the Second Extracellular Loop in Ligand Binding

Acknowledgments

Chapter 27: Glycoprotein Hormone Receptors: A Unique Paradigm for Ligand Binding and GPCR Activation

Introduction

Molecular Pathophysiology

Structure Function Relationships of the Glycoprotein Hormone Receptors

Conclusions and Perspectives

Chapter 28: Protease-Activated Receptors

Introduction

Mechanism of Activation

Protease-Activated Receptor Family

Roles of PARs In Vivo

Chapter 29: Constitutive and Regulated Signaling in Virus-Encoded 7TM Receptors

Virus-Encoded Proteins Are Developed through Targeted Evolution In Vivo

The Redundant Chemokine System Is an Optimal Target for Viral Exploitation

Multiple Virus-Encoded 7TM Receptors

Constitutive Signaling through Altered Pathways

Viral Receptors Recognize Multiple Ligands with Variable Function

Attempts To Identify the Function of Virus-Encoded Receptors In Vivo

Chapter 30: Frizzleds as G-Protein-Coupled Receptors for Wnt Ligands

Introduction

Wnt Signaling

Evidence for Frizzleds as G-Protein-Coupled Receptors

Perspective

Chapter 31: Agonist-Induced Desensitization and Endocytosis of G-Protein-Coupled Receptors

Introduction

General Processes of GPCR Regulation

Mechanisms of GPCR Desensitization and Endocytosis

Functional Consequences of GPCR Endocytosis

Chapter 32: Functional Role(s) of Dimeric Complexes Formed from G-Protein-Coupled Receptors

Acknowledgments

Chapter 33: The Role of Chemokine Receptors in HIV Infection of Host Cells

Introduction

HIV Entry

Coreceptor Use In Vivo

Env Domains Involved in Coreceptor Interactions

Coreceptor Domains Involved in HIV Infection

Receptor Presentation and Processing

Role of Signaling in HIV Infection

Summary

Acknowledgments

Chapter 34: Chemotaxis Receptor in Bacteria: Transmembrane Signaling, Sensitivity, Adaptation, and Receptor Clustering

Signaling at Periplasmic Ligand Binding Domain

Signaling at the Cytoplasmic Domain

Adaptation

Clustering of the Chemoreceptor and Sensitivity

Future Studies

Acknowledgment

Chapter 35: Overview: Function and Three-Dimensional Structures of Ion Channels

Introduction

Studies of Full-Length Ion Channels

General Pore Features Revealed by Bacterial Channels

Pore Helices: Electrostatic Aids to Permeation

Open Channels

Eukaryotic Ion Channels at High Resolution: Divide and Conquer

Ion Channel Accessory Subunits: Soluble and Transmembrane

The Future: Ion Channels as Electrosomes

Chapter 36: How Do Voltage-Gated Channels Sense the Membrane Potential?

Introduction

The Voltage-Sensing Gating Particle

S4 Is the Primary Voltage Sensor

Physical Models of Activation: Turning a Screw through a Bolt

Coupling Gating to S4 Voltage-Sensing Motions

Chapter 37: Ion Permeation: Mechanisms of Ion Selectivity and Block

Aqueous Pore

Ion Selectivity

Block

Chapter 38: Agonist Binding Domains of Glutamate Receptors: Structure and Function

Chapter 39: Nicotinic Acetylcholine Receptors

Function

Structure

Chapter 40: Small Conductance Ca2+-Activated K+ Channels: Mechanism of Ca2+ Gating

Introduction

Clones Encoding SK Channels

Biophysical and Pharmacological Profiles

Mechanism of Ca2+-gating

Pantophobiac After All

Chapter 41: Regulation of Ion Channels by Direct Binding of Cyclic Nucleotides

Introduction

The Cyclic Nucleotide-Gated Channels

Other Channels Directly Regulated by Cyclic Nucleotides

Section C: Horizontal Receptors

Chapter 42: Overview of Cytokine Receptors

Chapter 43: Growth Hormone and IL-4 Families of Hormones and Receptors: The Structural Basis for Receptor Activation and Regulation

Introduction

The Growth Hormone Family of Hormones and Receptors

Structural Basis for Receptor Homodimerization

Hormone Specificity and Cross-Reactivity Determine Physiological Roles

Hormone-Receptor Binding Sites

Receptor–Receptor Interactions

Hormone–Receptor Binding Energetics

Biological Implications of Transient Receptor Dimerization

A High-Affinity Variant of hGH (hGHv) Reveals an Altered Mode for Receptor Homodimerization

Site1 and Site2 Are Structurally and Functionally Coupled

IL-4 Hormone-Induced Receptor Activation

IL-4–α-Chain Receptor Interface

Binding of the γ-Chain Receptor

Comparisons of IL-4 with GH (PRL)

Concluding Remarks

Chapter 44: Erythropoietin Receptor as a Paradigm for Cytokine Signaling

Introduction

Biochemical Studies Supporting Preformed Dimers

Other Cytokine Receptor Superfamily Members

Conclusions

Acknowledgments

Chapter 45: A New Paradigm of Cytokine Action Revealed by Viral IL-6 Complexed to gp130: Implications for GCSF Interaction with GCSFR

Introduction

Receptor/Ligand Interactions

The gp130 System

Viral Interleukin-6

GCSF and GCSFR

Structure of the Viral IL-6–gp130 Complex

Site 1

The Site 2 Interface

The Site 3 Interface

Implications of the vIL-6–gp130 Tetramer Structure for the Active GCSF–GCSFR Extracellular Signaling Complex

Chapter 46: The Fibroblast Growth Factor (FGF) Signaling Complex

Introduction

FGF Polypeptides

FGFR Tyrosine Kinases

Heparan Sulfate

Oligomeric FGF–FGFR–HS Signaling Complex

Intracellular Signal Transduction by the FGFR Complex

Chapter 47: Structure of IFN-γ and Its Receptors

Chapter 48: Structure and Function of Tumor Necrosis Factor at the Cell Surface

Introduction

Structure of Tumor Necrosis Factor

TNF Receptors

Extracellular (Ligand Binding) Domains of TNF Family Receptors

Ligand–Receptor Complexes

Consequences of Ligand–Receptor Complex Formation

Receptor Preassociation

Conclusion

Chapter 49: The Mechanism of NGF Suggested by the NGF–TrkA-D5 Complex

Introduction

Neurotrophins

Trks

NGF–TrkA-D5 Complex

p75NTR

Chapter 50: The Mechanism of VEGFR Activation Suggested by the Complex of VEGF–flt1-D2

Introduction

Heparin-Binding Domain of VEGF

Receptor-Binding Domain of VEGF

VEGF Receptors

VEGF–flt1-D2 Complex

Chapter 51: Receptor–Ligand Recognition in the TGFβ Family as Suggested by the Crystal Structures of BMP-2–BR-IAec and TGFβ3–TR-IIec

Introduction

Ligand and Receptor Structures

Receptor–Ligand Complexes

BMP-2–BR-IAec Complex

Complex Formation with TGFβ Is Different than for BMP-2

Chapter 52: Insulin Receptor Complex and Signaling by Insulin

Introduction

Insulin Receptor Domain Structure

Binding Determinants of the IR

Insulin Signaling to Glucose Transport

Acknowledgment

Chapter 53: Structure and Mechanism of the Insulin Receptor Tyrosine Kinase

Introduction

Structural/Mechanistic Studies

Prospects

Acknowledgment

Chapter 54: What Does the Structure of Apo2L/TRAIL Bound to DR5 Tell Us About Death Receptors?

Introduction

Novel Features in the Structure of Apo2L/TRAIL

Apo2L/TRAIL:DR5 structures

Ligand-Independent Receptor Assembly

Intracellular Consequences of Ligand Binding

Conclusion

Section D: Membrane Proximal Events

Chapter 55: TNF Receptor Associated Factors

Chapter 56: Assembly of Signaling Complexes for TNF Receptor Family Molecules

Introduction

Receptor Aggregation

Raft Recruitment

Ubiquitination

Receptor Interactions

Conclusions

Chapter 57: Mechanisms of CD40 Signaling in the Immune System

Introduction

Signaling Pathways Triggered by CD40 Engagement

CD40 Signaling Is Mediated by TRAF-Dependent and TRAF-Independent Pathways

Chapter 58: Role of Lipid Domains in EGF Receptor Signaling

Introduction

Localization of the EGF Receptor to Lipid Rafts

Rafts and EGF-Receptor-Mediated Signaling

The EGF Receptor and Caveolin

Summary

Chapter 59: Structure and Function of B-Cell Antigen Receptor Complexes

Introduction

The Structure of the B Cell Antigen Receptor

Initiation of BCR Signaling Is Controlled by Redox Regulation

Chapter 60: Lipid-Mediated Localization of Signaling Proteins

Introduction

Protein Lipidation

Summary

Acknowledgments

Chapter 61: G-Protein Organization and Signaling

Introduction

G-Protein Molecular Organization

Structural Features of G Protein Activation

Structural Determinants of Receptor–G-Protein Specificity

Gα Interactions with Effector Molecules

Gβγ Interactions with Effector Molecules

Conclusions

Chapter 62: JAK–STAT Signaling

Introduction

Cytokine Signaling Proteins

JAK Structure and Localization

STAT Structure and Function

Inhibition of Cytokine Signaling

Summary

Acknowledgments

Chapter 63: Organization of Photoreceptor Signaling Complexes

INAD Organizes Signaling Complexes

INAD-Signaling Complexes in Phototransduction

Assembly, Targeting, and Anchoring of Signaling Complexes

Signaling Complexes in Vertebrate Photoreceptors

Chapter 64: Protein Localization in Negative Signaling

Introduction

The Role of CD28 and CTLA-4 in T-Cell Activation

Expression and Localization of CTLA-4 and CD28: Consequences for Receptor Function

Mechanisms of CTLA-4-Mediated Negative Signaling

Conclusions

Acknowledgments

Chapter 65: Transmembrane Receptor Oligomerization

Introduction

Tyrosine Kinase-Containing Receptors

Cytokine Receptors

Guanylyl Cyclase-Containing Receptors

Serine/Threonine Kinase-Containing Receptors

Tumor Necrosis Factor Receptors

Heptahelical Receptors (G-Protein-Coupled Receptors)

Concluding Remarks

PART II: TRANSMISSION: EFFECTORS AND CYTOSOLIC EVENTS

PART II: Introduction

Introduction to: Introduction

Section A: Protein Phosphorylation

Chapter 66: Eukaryotic Kinomes: Genomic Cataloguing of Protein Kinases and Their Evolution

Introduction

The Yeasts: Saccharomyces cerevisiae and Schizosaccharomyces pombe

Nematodes: Caenorhabditis elegans

Insects: Drosophila melanogaster

Vertebrates: Homo sapiens

Comparative Kinomics

Coda

Chapter 67: Modular Protein Interaction Domains in Cellular Communication

Introduction

Phosphotyrosine-Dependent Protein–Protein Interactions

Interaction Domains: A Common Theme in Signaling

Adaptors, Pathways, and Networks

Evolution of a Phospho-Dependent Docking Protein

Multisite Phosphorylation, Ubiquitination, and Switch-Like Responses

Summary

Acknowledgments

Chapter 68: Structures of Serine/Threonine and Tyrosine Kinases

Introduction

Structures of Protein Kinases

Structures of Inactive Protein Kinases

Summary

Chapter 69: Protein Tyrosine Kinase Receptor Signaling Overview

Introduction

PTK Subfamilies

Mechanism of Activation

Control of PTK Receptor Activity

Cross-Talk Between Signaling Pathways

PTK Receptors and Disease

Acknowledgments

Chapter 70: Signaling by the Platelet-Derived Growth Factor Receptor Family

Introduction

Platelet-Derived Growth Factors, Their Receptors, and Assembly of the PDGF Receptor Signaling Complex

Some Aspects of Regulation of the PDGF Receptor-Initiated Signaling

Chapter 71: EGF Receptor Family

Introduction

Domain Structure of ErbBs

Subcellular Localization of ErbB Proteins

ErbB-Induced Signaling Pathways

Negative Regulatory Pathways

Specificity of Signaling Through the ErbB Network

ErbB Proteins and Pathological Conditions

Chapter 72: IRS-Protein Scaffolds and Insulin/IGF Action

IRS-Proteins: The Beginnings

IRS-Proteins and Insulin Signaling

IRS-Protein Structure and Function

PI 3-Kinase Cascade

IRS-Protein Signaling in Growth, Nutrition, and Longevity

Interleukin-4 and IRS2 Signaling

Heterologous Regulation of IRS-Protein Signals

IRS2 and Pancreatic β-Cells

Summary

Chapter 73: Eph Receptors

Introduction

Ephs and Ephrins

Eph Receptor Signaling Via Cytoplasmic Protein Tyrosine Kinases

Eph Receptor Signaling Via Rho Family GTPases

Effects on Cell Proliferation

Eph Receptor Signaling through PDZ-Domain-Containing Proteins

Eph Receptors and Cell Adhesion

Ephrin Reverse Signaling

EphrinB Reverse Signaling Via Phosphotyrosine

EphrinB Reverse Signaling Via PDZ Domain Interactions

Summary

Chapter 74: Cytokine Receptor Superfamily Signaling

Cytokine Receptor Superfamily Signaling

Chapter 75: Negative Regulation of the JAK/STAT Signaling Pathway

Introduction

The Phosphatases

STAT Phosphatases

PIAS (Protein Inhibitors of Activated STATS)

SOCS (Suppressors of Cytokine Signaling) Family

Concluding Comments

Acknowledgments

Chapter 76: Activation of Oncogenic Protein Kinases

Introduction

Physiological Regulation of Protein Kinases

Activation of Protein Kinases by Retroviruses

Activation of Protein Kinases in Human Cancer

Oncogenic Protein Kinases as Targets for Therapy

Chapter 77: Protein Kinase Inhibitors

Signal Transduction Therapy

Protein Tyrosine Kinase Inhibitors

SER/THR Kinase Inhibitors

Chapter 78: Integrin Signaling: Cell Migration, Proliferation, and Survival

Introduction

Integrins Nucleate the Formation of Multi-Protein Complexes

Cell Migration: A Paradigm for Studying Integrin Signaling

Integrin Regulation of Cell Proliferation and Survival: Links to Cancer

Concluding Remarks

Acknowledgments

Chapter 79: Downstream Signaling Pathways: Modular Interactions

Introduction

General Properties of Interaction Modules

Roles in Signaling

Prospects

Chapter 80: Non-Receptor Protein Tyrosine Kinases in T-Cell Antigen Receptor Function

Introduction

T-Cell Antigen Receptor Structure

Src PTKs

Csk (c-Src PTK)

ZAP-70/Syk PTKs

Tec PTKs

Summary

Chapter 81: Cbl: A Physiological PTK Regulator

Introduction

Domains of Cbl Proteins

Sli-1: A Negative Regulator of RPTKs

PTK Downregulation by Polyubiquitylation

Cbl-Deficient Mice

Future Directions

Chapter 82: TGFβ Signal Transduction

Introduction

The Smad Pathway

Smads and the Ubiquitin–Proteasome System

Smad-Independent Signaling Pathways

Other Receptor Interacting Proteins

Chapter 83: MAP Kinases

Introduction

The ERK Module

Stress-Activated MAPKs, Part 1: SAPK/JNKs

Stress-Activated MAPKs, Part 2: p38 MAPKs

MAPKKs

MAPKKKs

MAPKKKKs

Summary

Acknowledgments

Chapter 84: Cytoskeletal Regulation: Small G-Protein–Kinase Interactions

Introduction

p21-Activated Kinases

Myotonic Dystrophy Kinase-Related Cdc42-Binding Kinase

Rho-Associated Kinase (ROK)

Acknowledgments

Chapter 85: Recognition of Phospho-Serine/Threonine Phosphorylated Proteins

Introduction

14-3-3 Proteins

FHA Domains

WW Domains

Leucine-Rich Repeats and WD40 Domains

Concluding Remarks

Acknowledgments

Chapter 86: Role of PDK1 in Activating AGC Protein Kinase

Introduction

Mechanism of Activation of PKB

PKB Is Activated by PDK1

Activation of Other Kinases by PDK1

Phenotype of PDK1 PKB- and S6K-Deficient Mice and Model Organisms

Hydrophobic Motif of AGC Kinases

Mechanism of Regulation of PDK1 Activity

Structure of the PDK1 Catalytic Domain

Concluding Remarks

Acknowledgments

Chapter 87: Regulation of Cell Growth and Proliferation in Metazoans by mTOR and the p70 S6 Kinase

Introduction

Functions of TOR

Signaling from TOR

Regulation of mTOR Activity (Fig. 2)

Chapter 88: AMP-Activated Protein Kinase

Introduction

Structure of the AMPK Complex

Regulation of the AMPK Complex

Regulation in Intact Cells and Physiological Targets

Medical Implications of the AMPK System

Acknowledgments

Chapter 89: Principles of Kinase Regulation

Introduction

Protein Kinase Structure

General Principles of Control

Regulatory Sites in Protein Kinase Domains

Conclusions

Chapter 90: Calcium/Calmodulin-Dependent Protein Kinase II

Introduction

Structure of CaMKII

Regulation by Autophosphorylation

Regulatory Roles of CaMKII in Neurons

Chapter 91: Glycogen Synthase Kinase 3

Introduction

The Substrate Specificity of GSK3

The Regulation of GSK3 Activity by Insulin and Growth Factors

GSK3 as a Drug Target

The Role of GSK3 in Embryonic Development

GSK3 and Cancer

Acknowledgments

Chapter 92: Protein Kinase C: Relaying Signals from Lipid Hydrolysis to Protein Phosphorylation

Introduction

Protein Kinase C Family

Regulation of Protein Kinase C

Function of Protein Kinase C

Summary

Acknowledgments

Chapter 93: The PIKK Family of Protein Kinases

Introduction

Overview of PIKK Family Members

Overall Architecture of PIKK Family Proteins

mTOR: A Key Regulator of Cell Growth

DNA-PKcs: At the Heart of the DNA Nonhomologous End-Joining Machinery

ATM and ATR: Signalers of Genome Damage

SMG-1: A Regulator of Nonsense-Mediated mRNA Decay

TRRAP: A Crucial Transcriptional Co-Activator

PIKK Family Members as Guardians of Nucleic Acid Structure, Function, and Integrity?

Acknowledgments

Chapter 94: Histidine Kinases

Chapter 95: Atypical Protein Kinases: The EF2/MHCK/ChaK Kinase Family

Introduction

Identification of an Atypical Family of Protein Kinases: EF2 Kinase, Myosin Heavy Chain Kinase and ChaK

The Structure of the Atypical Kinase Domain Reveals Similarity to Classical Protein Kinases and to Metabolic Enzymes with ATP-Grasp Domains

Substrate Specificity of Atypical Kinases

Regulation of Atypical Kinases

Functions of the Atypical Family of Protein Kinases

Acknowledgments

Chapter 96: Casein Kinase I and Regulation of the Circadian Clock

Introduction

double-time: A Casein Kinase I Homolog in Drosophila

Casein Kinase I in the Mammalian Clock

Casein Kinase I in the Neurospora Clock

Similarities and Differences of CKI Function in Different Clock Systems

Chapter 97: The Leucine-Rich Repeat Receptor Protein Kinases of Arabidopsis thaliana: A Paradigm for Plant LRR Receptors

Introduction

LRR Receptor Protein Kinases: The Genomic Point of View

LRR Receptor Protein Kinases: The Functional View

Summary

Chapter 98: Engineering Protein Kinases with Specificity for Unnatural Nucleotides and Inhibitors

Acknowledgments

Section B: Protein Dephosphorylation

Chapter 99: Overview of Protein Dephosporylation

Chapter 100: Protein Serine/Threonine Phosphatases and the PPP Family

Current Classification of Protein Serine/Threonine Phosphatases

Background

Evolution and Conserved Features of the PPP Family

Catalytic Activities of the PPP Family Members

Eukaryotic PPP Subfamilies

Domain and Subunit Structure of PPP Family Members

Medical Importance of the PPP Family

Acknowledgments

Chapter 101: The Structure and Topology of Protein Serine/Threonine Phosphatases

Introduction

Protein Serine/Threonine Phosphatases of the PPP Family

Protein Serine/Threonine Phosphatases of the PPM Family

Conclusions

Chapter 102: Naturally Occurring Inhibitors of Protein Serine/Threonine Phosphatases

Introduction

Effects of Inhibitors in Cell-Based Experiments

The Toxins Bind to the Active Sites of Protein Phosphatases

Chemical Synthesis of Protein Phosphatase Inhibitors

Microcystin Affinity Chromatography and Affinity Tagging

Avoiding the Menace of Toxins in the Real World Outside the Laboratory

Acknowledgments

Chapter 103: Protein Phosphatase 1 Binding Proteins

Introduction

Protein Phosphatase 1 (PP1)

PP1 Regulatory or Targeting Subunits

Conclusions

Acknowledgments

Chapter 104: Role of PP2A in Cancer and Signal Transduction

Introduction

Structure of PP2A

Subunit Interaction

Association of PP2A with Cellular Proteins

Alteration or Inhibition of PP2A Is Essential in Human Cancer Development

Mutation of Aα and Aβ Isoforms in Human Cancer

Differences between Aα and Aβ Subunits

PP2A and Wnt Signaling

PP2A and the MAP Kinase Pathway

Summary

Chapter 105: Serine/Threonine Phosphatase Inhibitor Proteins

Introduction

Protein Phosphatase 1 (PP1) Inhibitors

I-1, DARPP-32, and Other Phosphorylation-Dependent Phosphatase Inhibitors

Latent Phosphatase Complexes Activated by Inhibitor Phosphorylation

Inhibitors of Type-2 Serine/Threonine Phosphatases

Conclusions

Acknowledgments

Chapter 106: Calcineurin

Introduction

Enzymatic Properties

Structure

Regulation

Distribution and Isoforms

Functions

Muscle Differentiation

Conclusion

Chapter 107: Protein Serine/Threonine-Phosphatase 2C (PP2C)

Introduction

Regulation of the Stress-Activated MAP Kinase Cascades

Control of the CFTR Chloride Channel by PP2C

Plant Hormone Abscisic Acid Signaling

Fem-2: A Sex-Determining PP2C in Nematode

Stress-Responsive PP2Cs in Bacillus subtilis

Chapter 108: Overview of Protein Tyrosine Phosphatases

Background

Structural Diversity within the PTP Family

The Classical PTPs

The Dual Specificity Phosphatases (DSPs)

Regulation of PTP Function

Oxidation of PTPs in Tyrosine Phosphorylation-Dependent Signaling

Substrate Specificity of PTPs

PTPs and Human Disease

Perspectives

Acknowledgments

Chapter 109: Protein Tyrosine Phosphatase Structure and Mechanisms

Introduction

Introduction to the Protein Tyrosine Phosphatase Family

Structure

Mechanism

Regulation

Acknowledgments

Chapter 110: Bioinformatics: Protein Tyrosine Phosphatases

Introduction to Bioinformatics

Amino Acid Homology Among PTP Domains and Structure–Function Studies

Identification of the Genomic Complement of PTPs

Functional Aspects of PTPs in Health and Disease: Bioinformatics

Chapter 111: PTP Substrate Trapping

Introduction

Original C→S and D→A Substrate-Trapping Mutants

Second-Generation Trapping Mutants

Accessory or Noncatalytic Site Contributions to Substrate Recognition

New Twists on Trapping

Other Applications of Substrate Trapping Mutants

Chapter 112: Inhibitors of Protein Tyrosine Phosphatases

Introduction

Covalent PTP Modifiers

Oxyanions as PTP Inhibitors

pTyr Surrogates as PTP Inhibitors

Bidentate PTP Inhibitors

Other PTP Inhibitors

Concluding Remarks

Acknowledgment

Chapter 113: Regulating Receptor PTP Activity

Introduction

Regulation by Dimerization

Regulation by Phosphorylation

Regulation by D2 Domain

Chapter 114: CD45

Introduction

Structure

Function

Regulation

Acknowledgment

Chapter 115: Properties of the Cdc25 Family of Cell-Cycle Regulatory Phosphatases

Introduction

Physiological Functions of Cdc25

Regulation of Cdc25

Concluding Remarks

Chapter 116: Cell-Cycle Functions and Regulation of Cdc14 Phosphatases

Introduction

The Cdc14 Phosphatase Subgroup of PTPs

Budding Yeast Cdc14 is Essential for Exit from Mitosis

Fission Yeast Cdc14 Coordinates Cytokinesis with Mitosis

Potential Cell-Cycle Functions of Human Cdc14A and B

Chapter 117: MAP Kinase Phosphatases

Introduction

MAPK Phosphatases in Yeast

A MAPK Phosphatase in C. elegans

MAPK Phosphatases in Drosophila melanogaster

MAPK Phosphatases in Mammals

Summary

Chapter 118: SH2-Domain-Containing Protein–Tyrosine Phosphatases

History and Nomenclature

Structure, Expression, and Regulation

Biological Functions of Shps

Shp Signaling and Substrates

Determinants of Shp Specificity

Shps and Human Disease

Summary and Future Directions

Acknowledgments

Chapter 119: Insulin Receptor PTP: PTP1B

Introduction

PTP1B as a Bona Fide IR Phosphatase

PTP1B Gene Polymorphisms and Insulin Resistance

Insulin-Mediated Modulation of PTP1B

Genetic Evidence for Other PTP1B Substrates

Concluding Remarks

Chapter 120: Low-Molecular-Weight Protein Tyrosine Phosphatases

Introduction

Structures of LMW PTPases

Catalytic Mechanism

Inhibitors and Activators

Substrate Specificity, Regulation, and Biological Role

Acknowledgments

Chapter 121: STYX/Dead-Phosphatases

Introduction

Gathering Styx: Structure Implies Function

The Gratefully Undead: STYX/Dead-Phosphatases Mediate Phosphorylation Signaling

Conclusions

VOLUME 2

PART II: TRANSMISSION: EFFECTORS AND CYTOSOLIC EVENTS (CONTINUED FROM VOLUME 1)

Section C: Calcium Mobilization

Chapter 122: Phospholipase C

Introduction

PLC Anatomy

PLC Activation Mechanisms

PLC Physiology

Chapter 123: Inositol 1,4,5-trisphosphate 3-kinase and 5-phosphatase

Introduction

Type I InsP3 5-phosphatase

InsP3 3-kinase

Chapter 124: Cyclic ADP-ribose and NAADP

Introduction

Chapter 125: Sphingosine 1-phosphate

Introduction

Sphingolipid Metabolism

Activation of SPHK

Intracellular Target for SPP-mediated Ca2+ Release

Concluding Remarks

Acknowledgments

Chapter 126: Voltage-gated Ca2+ Channels

Introduction

Physiological Roles of Voltage-gated Ca2+ Channels

Ca2+ Current Types Defined by Physiological and Pharmacological Properties

Molecular Properties of Ca2+ Channels

Molecular Basis for Ca2+ Channel Function

Ca2+ Channel Regulation

Conclusion

Chapter 127: Store-operated Ca2+ Channels

Capacitative Calcium Entry

Store-operated Channels

Mechanism of Activation of Store-operated Channels

Summary

Chapter 128: Arachidonic Acid-regulated Ca2+ Channel

Introduction

Identification and Characterization of ARC Channels

Specific Activation of ARC Channels by Low Agonist Concentrations

Roles of ARC Channels and SOC/CRAC Channels in [Ca2+]i Signals: “Reciprocal Regulation”

Conclusions and Implications

Acknowledgments

Chapter 129: IP3 Receptors

Introduction

Chapter 130: Ryanodine Receptors

Function and Structure

Activation of Ryanodine Receptor Ca2+ Release Channels

Molecular Biology of Ryanodine Receptors

Chapter 131: Intracellular Calcium Signaling

The “Calcium Signaling Toolkit” and Calcium Homeostasis

Multiple Channels and Messengers Underlie Ca2+ Increases

Temporal Regulation of Ca2+ Signals

Spatial Regulation of Ca2+ Signals

Modulation of Ca2+ Signal Amplitude

Ca2+ as a Signal within Organelles and in the Extracellular Space

Chapter 132: Calcium Pumps

Introduction

Reaction Cycle of the SERCA and PMCA Pumps

The SERCA Pump

The PMCA Pump

Genetic Diseases Evolving Defects of Calcium Pumps

Chapter 133: Sodium/Calcium Exchange

Introduction

Two Families of PM Na+/Ca2+ Exchangers

Modes of Operation of the Na+/Ca2+ Exchangers

Regulation of NCX

Inhibition of NCX

Localization of the NCX

Physiolo