Sonnets: Three Volume Gift Set

Shakespeare's sonnets are thought to have been w见孙套却永艺练权ritten for 许打a private audience acros来自s several 局害燃比称固执鱼years, before being pu广卫blished in 1609.

• 装帧 精装
• ISBN 1906548005
• 书名 Sonnets: Three Volume Gift Set
• 页数 486页

简介

　　Shakespeare's sonnets are thought to have been written for a private audien来自ce across several years, before being published in 1609360百科.

　　条形码: 9781906548001

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

　　Shakespeare's sonnets are thou散ght to have been written for a private audience across several years, before being published in 1609. The ver服学病些ses that compose the sonnets are often subversive, elusive, and int她逐染联接劳景响光imate, shaping an eroti统确普烧照回掌论艺喜c body of poetr界科行y in the pursuit of the depths and parameters of emotion. He seems to have planned c革ontrasting 剂布度免衣布孙加series--bitter sequences of lust and recrimination h几儿今味aunted by a 扬合比评专married "d绍起危握仍察们石民路ark lady," lyrics praising yout皮概攻部校h and beauty addressed to a "fair youth," and allegorical contempla似天动二tions of Gre材致支达ek myth.

　　Shakespeare's so保副位具龙把nnets are thought to have been written for a pr织员娘宜会胶领儿西兴指ivate audie何鲜带nce across several years, before being published in 1609. The verses that compose the sonnets are often subvers比决造均总入代杀万ive, 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.

　　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