Bradshaw / Dennis Functioning of Transmembrane Receptors in Signaling Mechanisms

Cell Signaling Collection
1. Auflage 2011
ISBN: 978-0-12-382212-3
Verlag: Elsevier Science & Techn.
Format: PDF
Kopierschutz: 1 - PDF Watermark

E-Book, Englisch, 456 Seiten, Web PDF

A primary component of cell signaling research, this title covers the principal membrane-bound receptor families, including their structural organization. Written and edited by experts in the field, this book provides up-to-date research on transmembrane signaling entities and their initiating responses following extracellular stimulation. - Articles written and edited by experts in the field - Thematic volume covering effectors, cytosolic events, nuclear, and cytoplasmic events - Up-to-date research on signaling systems and mutations in transcription factors that provide new targets for treating disease

Autoren/Hrsg.

Bradshaw, Ralph A.

Dennis, Edward A.

Inhaltsverzeichnis

1;Front Cover;1
2;Functioning of Transmembrane Receptors in Cell Signaling;4
3;Copyright Page;5
4;Editorial Advisory Board;6
5;Contents;8
6;Preface;12
7;Contributors;14
8;Section A: Overview;18
8.1;Chapter 1: Transmembrane Receptors and Their Signaling Properties;20
8.1.1;Origins of Cell Signaling Research;20
8.1.2;Transmembrane Receptors;21
8.1.3;Focus and Scope of this Volume;23
8.1.4;References;24
9;Section B: Biophysical Principles and General Properties;26
9.1;Chapter 2: Structural and Energetic Basis of Molecular Recognition;28
9.1.1;Introduction;28
9.1.2;Principles of Binding;28
9.1.3;Non-Specific Association with Membrane Surfaces;29
9.1.4;Protein – Protein Interactions;29
9.1.5;Prospects;29
9.1.6;References;30
9.2;Chapter 3: Free Energy Landscapes in Protein – Protein Interactions;32
9.2.1;Thermodynamics of Protein – Protein Interactions;32
9.2.2;Interaction Kinetics;33
9.2.3;Dissociation of a Protein Complex;35
9.2.4;The Modular Structure of Protein – Protein Binding Sites;35
9.2.5;Interaction Between Membrane Anchored Proteins;36
9.2.6;Summary;37
9.2.7;References;37
9.3;Chapter 4: Molecular Sociology;40
9.3.1;Transmembrane Signaling Paradigms;40
9.3.2;Structural Basis of Protein – Protein Recognition;43
9.3.3;Conclusion;44
9.3.4;References;44
9.4;Chapter 5: FRET Analysis of Signaling Events in Cells;46
9.4.1;Introduction;46
9.4.2;Fluorescent Probes for Fret;46
9.4.3;Fret Detection Techniques;47
9.4.4;Conclusions and Prospects;49
9.4.5;References;49
9.5;Chapter 6: Structures of Serine/Threonine and Tyrosine Kinases;52
9.5.1;Introduction;52
9.5.2;Structural Features of Serine/Threonine and Tyrosine Kinases;52
9.5.3;Regulation of Serine/Threonine and Tyrosine Kinase Activity;53
9.5.4;Prospects;55
9.5.5;Acknowledgements;55
9.5.6;References;55
9.6;Chapter 7: Large-Scale Structural Analysis of Protein Tyrosine Phosphatases;58
9.6.1;Overview;58
9.6.2;Structural Coverage of the Family;58
9.6.3;Structural Features;58
9.6.4;A Shared Catalytic Mechanism;60
9.6.5;Receptor Dimerization;62
9.6.6;Endnote;62
9.6.7;References;63
9.7;Chapter 8: Transmembrane Receptor Oligomerization;64
9.7.1;Introduction;64
9.7.2;Tyrosine Kinase-Containing Receptors;65
9.7.3;Cytokine Receptors;65
9.7.4;Guanylyl Cyclase-Containing Receptors;67
9.7.5;Serine/Threonine Kinase-Containing Receptors;67
9.7.6;Tumor Necrosis Factor Receptors;67
9.7.7;Heptahelical Receptors (G-Proteincoupled Receptors);68
9.7.8;Concluding Remarks;68
9.7.9;References;68
10;Section C: Major Receptor Families;70
10.1;Part 1: Receptor Tyrosine Kinases;72
10.1.1;Chapter 9: Protein Tyrosine Kinase Receptor Signaling Overview;74
10.1.1.1;Introduction;74
10.1.1.2;PTK Subfamilies;74
10.1.1.3;Mechanism of Activation;75
10.1.1.4;Control of PTK Receptor Activity;78
10.1.1.5;Cross-Talk Between Signaling Pathways;78
10.1.1.6;PTK Receptors and Disease;79
10.1.1.7;Acknowledgements;80
10.1.1.8;References;80
10.1.2;Chapter 10: Receptor Tyrosine Kinase Signaling and Ubiquitination;82
10.1.2.1;Introduction;82
10.1.2.2;The Ubiquitin Conjugation System;82
10.1.2.3;RTK Signaling and Endocytosis are Molecularly Linked;82
10.1.2.4;Ubiquitination in RTK Endocytosis;83
10.1.2.5;Ubiquitination of Effector Proteins in RTK Signaling;84
10.1.2.6;Concluding Remarks and Future Perspectives;84
10.1.2.7;Acknowledgements;84
10.1.2.8;References;85
10.1.3;Chapter 11: Insulin Receptor Complex and Signaling by Insulin;86
10.1.3.1;Introduction;86
10.1.3.2;Insulin Receptor Domain Structure;86
10.1.3.3;Binding Determinants of the Insulin Receptor;87
10.1.3.4;Insulin Signaling to Glucose Transport;88
10.1.3.5;Acknowledgements;90
10.1.3.6;References;90
10.1.4;Chapter 12: Structure and Mechanism of the Insulin Receptor Tyrosine Kinase;92
10.1.4.1;Introduction;92
10.1.4.2;Protein Recruitment to the Activated Insulin Receptor;93
10.1.4.3;Prospects;97
10.1.4.4;Acknowledgements;97
10.1.4.5;References;97
10.1.5;Chapter 13: IRS-Protein Scaffolds and Insulin/IGF Action in Central and Peripheral Tissues;100
10.1.5.1;Introduction;100
10.1.5.2;Insulin, Igfs, and their Receptors;100
10.1.5.3;Insulin Receptor Substrates;101
10.1.5.4;Dysregulation of IRS-Protein Signaling;104
10.1.5.5;Summary and Perspectives;107
10.1.5.6;References;107
10.1.6;Chapter 14: The Epidermal Growth Factor Receptor Family;112
10.1.6.1;Introduction;112
10.1.6.2;Structure and Activation of ERBB Receptors and their Ligands;112
10.1.6.3;ERBB-Induced Signaling Pathways;114
10.1.6.4;Specificity of Signaling Through the ERBB Network;114
10.1.6.5;Attenuation of the ERBB Signaling Network;115
10.1.6.6;ERBB Proteins and Pathological Conditions;116
10.1.6.7;Acknowledgements;117
10.1.6.8;References;117
10.1.7;Chapter 15: Epidermal Growth Factor Kinases and their Activation in Receptor Mediated Signaling;120
10.1.7.1;Introduction;120
10.1.7.2;EGFR Signaling Network Pathways;121
10.1.7.3;Structural Biology of Receptor Fragments;122
10.1.7.4;Conformations of the ECD Fragments of ErbB Receptors;122
10.1.7.5;Kinase Domain Fragment Structures;122
10.1.7.6;Biophysical Studies of ErbB Activation at the Cell Surface;123
10.1.7.7;ErbB Receptors Exist as Predominantly Pre-Formed Dimers in Cells;123
10.1.7.8;Beyond Dimers: A Ligand-Induced EGFR Tetramer is Formed During Activation;123
10.1.7.9;Activation-Dependent Higher-Order ErbB Oligomers in Cancer Cells;124
10.1.7.10;New Paradigm in ErbB Activation and Signaling;125
10.1.7.11;References;125
10.1.8;Chapter 16: Role of Lipid Domains in EGF Receptor Signaling;128
10.1.8.1;Introduction;128
10.1.8.2;Studying Lipid Rafts;129
10.1.8.3;Localization of the EGF Receptor in Lipid Rafts;129
10.1.8.4;Rafts and EGF Receptor-Mediated Signaling;130
10.1.8.5;The EGF Receptor and Caveolin;131
10.1.8.6;References;132
10.1.9;Chapter 17: Signaling by the Platelet-Derived Growth Factor Receptor Family;134
10.1.9.1;Platelet-Derived Growth Factor Isoforms;134
10.1.9.2;Physiological Function of PDGF;134
10.1.9.3;Activation of Platelet-Derived Growth Factor Receptors and Regulation of Kinase Activity;135
10.1.9.4;Interaction of the PDGF Receptors with Downstream Signal Transduction Molecules;135
10.1.9.5;Regulation and Modulation of PDGF Receptor Signaling;137
10.1.9.6;Conclusions;139
10.1.9.7;Acknowledgements;139
10.1.9.8;References;139
10.1.10;Chapter 18: The Fibroblast Growth Factor (FGF) Signaling Complex;142
10.1.10.1;Introduction;142
10.1.10.2;FGF Polypeptides;142
10.1.10.3;FGFR Tyrosine Kinases;143
10.1.10.4;Heparan Sulfate and Klothos;143
10.1.10.5;The Oligomeric FGF – FGFR – HS Signaling Complex;144
10.1.10.6;Intracellular Signal Transduction by the FGFR Complex;145
10.1.10.7;References;146
10.1.11;Chapter 19: The Mechanism of NGF Signaling Suggested by the p75 and TrkA Receptor Complexes;150
10.1.11.1;Introduction;150
10.1.11.2;Neurotrophins;150
10.1.11.3;NGF – TrkA Complexes;152
10.1.11.4;NGF – p75 NTR Complexes;153
10.1.11.5;Neurotrophin Signaling Excursions;154
10.1.11.6;Prospects for Ternary Receptor Complexes;155
10.1.11.7;Neurotrophin Therapeutics;155
10.1.11.8;References;155
10.1.12;Chapter 20: The Mechanism of VEGFR Activation by VEGF;160
10.1.12.1;Structural Characterization of VEGF Family Members;160
10.1.12.2;Structural Characterization of VEGFRs;161
10.1.12.3;Pdgfr and Analogies to VEGFRs;162
10.1.12.4;VEGF Co-Receptors: Neuropilins;163
10.1.12.5;Conclusion;163
10.1.12.6;References;164
10.1.13;Chapter 21: Mechanisms and Functions of Eph Receptor signaling;166
10.1.13.1;Introduction;166
10.1.13.2;Eph/Ephrin Protein Structures and Signaling Concepts;166
10.1.13.3;Regulation of Eph/Ephrin Signaling Activity;168
10.1.13.4;Disruption of Cell – Cell Contacts and Internalization of Signaling Complexes;168
10.1.13.5;Eph (Forward) Signaling;168
10.1.13.6;Ephrin (Reverse) Signaling;169
10.1.13.7;Cross-Talk with Other Signal Pathways;169
10.1.13.8;Eph/Ephrin Facilitated Cell - Cell Communication During Vertebrate Development;170
10.1.13.9;Ephs in Oncogenesis: De-Regulated Cell Positioning During Invasion and Metastasis;170
10.1.13.10;References;171
10.2;Part 2: Cytokine Receptors;174
10.2.1;Chapter 22: Overview of Cytokine Receptors;176
10.2.2;Chapter 23: Cytokine Receptor Signaling;178
10.2.2.1;Introduction;178
10.2.2.2;Generation of High-Affinity Cytokine – Receptor Complexes;178
10.2.2.3;Architecture of Extracellular Domain;178
10.2.2.4;Receptor Signaling-Utilizing EPO-R as a Model;180
10.2.2.5;Activation of the JAK Tyrosine Kinases;180
10.2.2.6;JAK1;181
10.2.2.7;JAK2;181
10.2.2.8;JAK3;181
10.2.2.9;TYK2;182
10.2.2.10;Recruitment and Activation of STAT Transcription Factors;182
10.2.2.11;STAT1;182
10.2.2.12;STAT2;182
10.2.2.13;STAT3;184
10.2.2.14;STAT4;184
10.2.2.15;STAT5;184
10.2.2.16;STAT6;185
10.2.2.17;Participation of the Phoshatidylinositol 3' Kinase Pathway in Cell Survival Signaling;185
10.2.2.18;ERK, JNK and P38 are All Activated Downstream of Cytokine Receptor Engagement;185
10.2.2.19;Negative Regulation;186
10.2.2.20;Developmental Regulation of the Cytokine Signaling Pathway;186
10.2.2.21;Involvement of the Cytokine Signaling Pathway in Human Disease;187
10.2.2.22;Concluding Remarks;188
10.2.2.23;Acknowledgements;188
10.2.2.24;References;190
10.2.3;Chapter 24: Growth Hormone and Prolactin Family of Hormones and Receptors: The Structural Basis for Receptor Activation and Regulation;194
10.2.3.1;Introduction;194
10.2.3.2;The Growth Hormone Family of Hormones and Receptors;194
10.2.3.3;Triggering GH and PRL Receptor Activation: Revision to the Dogma;194
10.2.3.4;An Unanticipated Role for Cytokine Hormones as Transcriptional Enhancers;195
10.2.3.5;Structural Basis for Receptor Homodimerization;196
10.2.3.6;Hormone Specificity and Cross-Reactivity Determines Physiological Roles;198
10.2.3.7;Concluding Remarks;198
10.2.3.8;References;199
10.2.4;Chapter 25: Erythropoietin Receptor as a Paradigm for Cytokine Signaling;202
10.2.4.1;Introduction;202
10.2.4.2;Structural Studies on EPOR;202
10.2.4.3;Biochemical Studies Supporting Preformed Dimers;205
10.2.4.4;Other Cytokine Receptor Superfamily Members;207
10.2.4.5;Conclusions;207
10.2.4.6;Acknowledgements;208
10.2.4.7;References;208
10.2.5;Chapter 26: Structure of IFN. and its Receptors;210
10.2.5.1;References;212
10.3;Part 3: G Protein-Coupled Receptors;214
10.3.1;Chapter 27: Structures of Heterotrimeric G Proteins and their Complexes;216
10.3.1.1;Introduction;216
10.3.1.2;G Subunits;216
10.3.1.3;G-Effector Interactions;219
10.3.1.4;GTP Hydrolysis by G and its Regulation by GAPs;219
10.3.1.5;Gß. Dimers;221
10.3.1.6;Receptor-Independent Regulators of G Protein Activation;222
10.3.1.7;Ga – GPCR Interactions;222
10.3.1.8;References;223
10.3.2;Chapter 28: G Protein-Coupled Receptor Structures;226
10.3.2.1;Introduction;226
10.3.2.2;Classification;226
10.3.2.3;Basic Concept of GPCR; Heterotrimeric G Proteins; The Vast Complexity of GPCR Signaling;228
10.3.2.4;Models for Receptor Activation;230
10.3.2.5;Structures of Extracellular Domains of GPCRs;230
10.3.2.6;Structures Probing the Inactive State(S): Ligand Entry, Binding, and Modes for Activity Blocking;230
10.3.2.7;Structure of Active State(S);232
10.3.2.8;Acknowledgements;234
10.3.2.9;References;234
10.3.3;Chapter 29: Heterotrimeric G-Protein Signaling at Atomic Resolution;236
10.3.3.1;Introduction;236
10.3.3.2;Architecture and Switching Mechanism of the Ga Subunits;236
10.3.3.3;Insight into the GTP Hydrolytic Mechanism from an Unexpected Transition State Mimic;237
10.3.3.4;Gß. with and without Ga;237
10.3.3.5;Phosducin and Gß.;238
10.3.3.6;GSa and Adenylyl Cyclase;238
10.3.3.7;Filling in the Gap;239
10.3.3.8;Visual Fidelity;239
10.3.3.9;What Structures May Follow;239
10.3.3.10;References;239
10.3.4;Chapter 30: Structure and Function of G-Protein-Coupled Receptors: Lessons from Recent Crystal Structures;242
10.3.4.1;Introduction;242
10.3.4.2;Recent Advances in Structural Studies of G-Protein-Coupled Receptors;242
10.3.4.3;Crystal Structures of Human ß2AR;244
10.3.4.4;Understanding Ligand Binding Specificity in GPCRs;245
10.3.4.5;Structural Basis of the Active State;245
10.3.4.6;References;246
10.3.5;Chapter 31: Chemokines and Chemokine Receptors: Structure and Function;248
10.3.5.1;Introduction;248
10.3.5.2;Chemokine Structure and Function;248
10.3.5.3;Chemokine Receptors;250
10.3.5.4;References;251
10.3.6;Chapter 32: The ß2 Adrenergic Receptor as a Model for G-Protein-Coupled Receptor Structure and Activation by Diffusible Hormone;254
10.3.6.1;Introduction;254
10.3.6.2;A Model System for GPCRs Recognizing Diffusible Ligands;254
10.3.6.3;Conformational States on the Pathway to Activation;255
10.3.6.4;Crystal Structures of the Human ß2AR;256
10.3.6.5;Comparison to the Structure of Rhodopsin;256
10.3.6.6;Mechanism of Agonist-Induced Activation;257
10.3.6.7;References;259
10.3.7;Chapter 33: Agonist-Induced Desensitization and Endocytosis of G-protein-Coupled Receptors;262
10.3.7.1;General Processes of GPCR Regulation;262
10.3.7.2;Mechanisms of GPCR Desensitization and Endocytosis;263
10.3.7.3;Functional Consequences of GPCR Endocytosis;265
10.3.7.4;References;266
10.3.8;Chapter 34: Functional Role(s) of Dimeric Complexes Formed from G-Protein-Coupled Receptors;270
10.3.8.1;Introduction;270
10.3.8.2;Historical Perspective;270
10.3.8.3;Heterodimerization Alters Receptor Function;272
10.3.8.4;Receptor Heterodimerization in Physiology and Pathology;274
10.3.8.5;Conclusion;276
10.3.8.6;Acknowledgements;276
10.3.8.7;References;276
10.4;Part 4: TGFß Receptors;280
10.4.1;Chapter 35: Receptor – Ligand Recognition in the TGFß Superfamily as Suggested by Crystal Structures of their Ectodomain Comple;282
10.4.1.1;Introduction;282
10.4.1.2;Ligand Structures;282
10.4.1.3;Receptor Structures;283
10.4.1.4;Receptor – Ligand Complexes;284
10.4.1.5;Concluding Remarks;287
10.4.1.6;Notes;287
10.4.1.7;References;288
10.4.2;Chapter 36: TGFß Signal Transduction;290
10.4.2.1;Introduction;290
10.4.2.2;TGFß Ligands;290
10.4.2.3;Receptors;291
10.4.2.4;Activation and Regulation of Receptors;292
10.4.2.5;The Smads: Effectors of TGFß Family Transcriptional Programs;293
10.4.2.6;Smad Activation;295
10.4.2.7;Regulation of TGFß Signal Transduction by Inhibitory Smads;295
10.4.2.8;Smads are DNA-Binding Proteins;296
10.4.2.9;Smads Cooperate with DNA-Binding Partners;296
10.4.2.10;Smads Interact with Transcription Co-Activators and Repressors;297
10.4.2.11;Non-Smad Signaling Pathways;297
10.4.2.12;References;298
10.4.3;Chapter 37: The Smads;302
10.4.3.1;History and Categorization: R-Smads, Co-Smads, and I-Smads;302
10.4.3.2;Smad Regulation by Receptors and Nucleocytoplasmic Shuttling;302
10.4.3.3;Transcriptional Regulation by Smads;302
10.4.3.4;Downregulation and Cross-Regulation of Smads;304
10.4.3.5;Function of Smads In Vivo: Gain of Function and Loss of Function Experiments;304
10.4.3.6;Acknowledgements;305
10.4.3.7;References;305
10.5;Part 5: TNF Receptors;308
10.5.1;Chapter 38: Structure and Function of Tumor Necrosis Factor (TNF) at the Cell Surface;310
10.5.1.1;Introduction;310
10.5.1.2;Structural Features;310
10.5.1.3;Signaling Pathways and Regulation;315
10.5.1.4;Biological Functions;315
10.5.1.5;Therapeutics and Future Expectations;316
10.5.1.6;Acknowledgement;317
10.5.1.7;References;317
10.5.2;Chapter 39: Tumor Necrosis Factor Receptor-Associated Factors in Immune Receptor Signal Transduction;322
10.5.2.1;Introduction;322
10.5.2.2;Discovery of TRAF Proteins;322
10.5.2.3;Biological Functions of TRAF Proteins;322
10.5.2.4;Domain Organizations and Structures of TRAFs;323
10.5.2.5;The Unique TRAF6;324
10.5.2.6;TRAF Signaling and LYS63 Linked Polyubiquitination;325
10.5.2.7;Regulation of TRAF Signaling;326
10.5.2.8;Summary and Perspectives;326
10.5.2.9;Acknowledgement;326
10.5.2.10;References;326
10.6;Part 6: Guanylyl Cyclases;330
10.6.1;Chapter 40: Guanylyl Cyclases;332
10.6.1.1;Historical Perspective;332
10.6.1.2;Overview of Mammalian Guanylyl Cyclases;332
10.6.1.3;Soluble Guanylyl Cyclase, Nitric Oxide, and Nitric Oxide Synthase;332
10.6.1.4;GC-A/NPR-A/NPR1;334
10.6.1.5;GC-B/NPR-B/NPR2;335
10.6.1.6;NPR-C/NPR-3;335
10.6.1.7;GC-C/STAR;335
10.6.1.8;GC-D;336
10.6.1.9;GC-E/RET-GC1 and GC-F/RET-GC2;336
10.6.1.10;GC-G;336
10.6.1.11;Acknowledgements;337
10.6.1.12;References;337
11;Section D: Other Transmembrane Signaling Proteins;342
11.1;Part 1: Adhesion Molecules;344
11.1.1;Chapter 41: Mechanistic Features of Cell-Surface Adhesion Receptors;346
11.1.1.1;Mechanosensory Mechanisms;346
11.1.1.2;Cell – Cell Adhesions/Adherens Junctions;347
11.1.1.3;T Cell Co-Stimulation;348
11.1.1.4;Axon Guidance and Neural Development;350
11.1.1.5;Conclusions;351
11.1.1.6;References;351
11.1.2;Chapter 42: Structural Basis of Integrin Signaling;354
11.1.2.1;Introduction;354
11.1.2.2;Structure;354
11.1.2.3;Quaternary Changes;355
11.1.2.4;Tertiary Changes;355
11.1.2.5;Tail Interactions;356
11.1.2.6;Concluding Remarks;356
11.1.2.7;References;356
11.1.3;Chapter 43: Carbohydrate Recognition and Signaling;358
11.1.3.1;Introduction;358
11.1.3.2;Biological Roles of Carbohydrate Recognition;358
11.1.3.3;Carbohydrate Structure and Diversity;358
11.1.3.4;Lectins and Carbohydrate Recognition;359
11.1.3.5;Carbohydrate-Mediated Signaling;359
11.1.3.6;Conclusions;362
11.1.3.7;References;362
11.2;Part 2: Ion Channels;366
11.2.1;Chapter 44: An Overview of Ion Channel Structure;368
11.2.1.1;Introduction;368
11.2.1.2;Obtaining Three-Dimensional Structures of Channels: Methods and Challenges;369
11.2.1.3;Prokaryotic Ion Channels: Gateways to Full Length Channel Structure;370
11.2.1.4;Open Channels;370
11.2.1.5;Eukaryotic Ion Channels at High Resolution: Whole Channels and Exploitation of Modular Structure to Divide and Conquer;371
11.2.1.6;Divide and Conquer: Exploitation of the Modular Nature of Ion Channel Structure;372
11.2.1.7;Ion Channel Complexes;373
11.2.1.8;References;373
11.2.2;Chapter 45: Voltage-Gated Calcium Channels;376
11.2.2.1;Physiological Roles of Voltage Gated Ca2+ Channels;376
11.2.2.2;Ca2+ Current Types Defined by Physiological and Pharmacological Properties;377
11.2.2.3;Molecular Properties of Ca2+ Channels;377
11.2.2.4;Ca2+ Channel Signaling Complexes;380
11.2.2.5;The Effector Checkpoint Model of Ca2+ Channel Regulation;383
11.2.2.6;References;383
11.2.3;Chapter 46: Store-Operated Calcium Channels;390
11.2.3.1;Store-Operated or Capacitative Calcium Entry;390
11.2.3.2;Store-Operated Channels – TRPs?;390
11.2.3.3;Major Players Identified: STIM and ORAI/CRACM;391
11.2.3.4;Signaling to Store-Operated Channels;391
11.2.3.5;References;392
11.2.4;Chapter 47: Intracellular Calcium Signaling;394
11.2.4.1;The “Calcium Signaling Toolkit” and Calcium Homeostasis;394
11.2.4.2;Channels Underlying Ca2+ Increase;395
11.2.4.3;Temporal Regulation of Ca2+ Signals;396
11.2.4.4;Spatial Regulation of Ca2+ Signals;397
11.2.4.5;References;398
11.2.5;Chapter 48: Cyclic Nucleotide-Regulated Cation Channels;400
11.2.5.1;Introduction;400
11.2.5.2;General Features of Cyclic Nucleotide-Regulated Cation Channels;400
11.2.5.3;CNG Channels;401
11.2.5.4;HCN Channels;402
11.2.5.5;Acknowledgement;403
11.2.5.6;References;403
11.3;Part 3: Immunoglobulin Receptors;406
11.3.1;Chapter 49: Immunoglobulin – Fc Receptor Interactions;408
11.3.1.1;Introduction;408
11.3.1.2;Immunoglobulin Structure;408
11.3.1.3;Fc Receptors and their Structures;409
11.3.1.4;IgG – Receptor Interactions;410
11.3.1.5;IgE – Receptor Interactions;411
11.3.1.6;IgA – Receptor Interactions;412
11.3.1.7;Conclusions;413
11.3.1.8;References;413
11.3.2;Chapter 50: T Cell Receptor/pMHC Complexes;416
11.3.2.1;TCR Generation and Architecture;416
11.3.2.2;Peptide Binding to MHC Class IA and II;417
11.3.2.3;TCR/pMHC Interaction;417
11.3.2.4;Orientation of the TCR in TCR/PMHC Complexes;417
11.3.2.5;Peptide Recognition by the TCR CDR Loops;418
11.3.2.6;Discrepancy Between Magnitude of Structural Changes and Biological Outcomes;419
11.3.2.7;Role of Bound Water in TCR/pMHC Recognition;420
11.3.2.8;Conclusions and Future Perspectives;420
11.3.2.9;References;421
11.3.3;Chapter 51: NK Receptors;424
11.3.3.1;Immunoreceptors;424
11.3.3.2;Natural Killer Cells;424
11.3.3.3;IG-Type NK Receptors: KIR;427
11.3.3.4;Other IG-Type Receptors on NK Cells;428
11.3.3.5;C-Type Lectin-Like NK Receptors: LY49A;428
11.3.3.6;C-Type Lectin-Like NK Receptors: NKG2D;429
11.3.3.7;References;429
11.3.4;Chapter 52: Toll-Like Receptors – Structure and Signaling;432
11.3.4.1;Structure of TLR3;432
11.3.4.2;The dsRNA Binding Site in hTLR3;432
11.3.4.3;TLR4;432
11.3.4.4;MD-2;434
11.3.4.5;TLR1 – TLR2 Dimerization by a Tri-Acylated Lipopeptide;435
11.3.4.6;Signaling;435
11.3.4.7;Acknowledgements;436
11.3.4.8;References;436
11.3.5;Chapter 53: Toll Family Receptors;438
11.3.5.1;Introduction;438
11.3.5.2;Structure – Function of Toll Receptors;438
11.3.5.3;Signaling by Toll Family Receptors;440
11.3.5.4;References;442
12;Index;444