Dennis / Bradshaw Intercellular Signaling in Development and Disease

Cell Signaling Collection
1. Auflage 2011
ISBN: 978-0-12-382216-1
Verlag: Elsevier Science & Techn.
Format: PDF
Kopierschutz: 1 - PDF Watermark

E-Book, Englisch, 540 Seiten, Web PDF

Required reading for anyone involved in cell signaling research with articles written and edited by experts in the field. This title covers disease states such as lymphoid leukemia, breast cancer, pulmonary fibrosis, systemic sclerosis, andinflammatory bowel disease, along with up-to-date research on signaling systems and mutations intranscription factors that provide new targets for treating disease. - Articles written and edited by experts in the field - Thematic volume covering disease states such as lymphoid leukemia, breast cancer, pulmonary fibrosis, systemic sclerosis, and inflammatory bowel disease - Up-to-date research on signaling systems and mutations in transcription factors that provide new targets for treating disease

Autoren/Hrsg.

Dennis, Edward A.

Bradshaw, Ralph A.

Inhaltsverzeichnis

1;Front Cover;1
2;Intercellular Signaling in Development and Disease;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: Signaling in Development and Disease;20
8.1.1;Origins of Cell Signaling Research;20
8.1.2;Receptors and Intracellular Signaling;21
8.1.3;Intercellular Signaling;23
8.1.4;Focus and Scope of this Volume;24
8.1.5;References;24
9;Section B: Cell-Cell Signaling;26
9.1;Chapter 2: Overview of Cell – Cell and Cell – Matrix Interactions;28
9.1.1;References;29
9.2;Chapter 3: Integrin Signaling: Cell Migration, Proliferation, and Survival;30
9.2.1;Introduction;30
9.2.2;Integrins Nucleate the Formation of Dynamic Multi-Protein Complexes;30
9.2.3;Cell Migration: A Paradigm for Studying Integrin Signaling;32
9.2.4;Lamellipodia Extension, and Adhesion Formation and Stabilization at the Leading Edge;32
9.2.5;Maturation, Detachment, and Release of Adhesions;33
9.2.6;Growth Factor Receptor and Integrin Signaling-Synergistic Regulation of Cell Proliferation and Survival;33
9.2.7;Integrin Signals and Links to Cancer;34
9.2.8;Concluding Remarks;35
9.2.9;Acknowledgements;35
9.2.10;References;35
9.3;Chapter 4: The Focal Adhesion: A Network of Molecular Interactions;40
9.3.1;Introduction;40
9.3.2;Integrin Activation;40
9.3.3;Adhesion Strengthening;40
9.3.4;Intracellular Signaling and Molecular Scaffolds;41
9.3.5;Focal Adhesion Turnover;42
9.3.6;Focal Adhesions and Gene Expression;43
9.3.7;The Future;43
9.3.8;Acknowledgements;43
9.3.9;References;43
9.4;Chapter 5: Cadherin Regulation of Adhesive Interactions;46
9.4.1;Introduction;46
9.4.2;The Cadherin Family;46
9.4.3;Cadherin Structure – Function Relationships;49
9.4.4;Multiple Modes for Regulating Cadherin Adhesive Activity;51
9.4.5;Conclusions and Perspectives;54
9.4.6;Acknowledgements;54
9.4.7;References;55
9.5;Chapter 6: In vivo Functions of Heterotrimeric G Proteins;60
9.5.1;Introduction;60
9.5.2;Development;60
9.5.3;Central Nervous System;60
9.5.4;Immune System;63
9.5.5;Heart;63
9.5.6;Sensory Systems;63
9.5.7;Hemostasis;63
9.5.8;Conclusions;64
9.5.9;References;64
9.6;Chapter 7: G-Protein Signaling in Chemotaxis;68
9.6.1;Introduction;68
9.6.2;Chemotaxis: Membrane Extensions, Directional Sensing, and Polarization;68
9.6.3;Chemoattractant Signaling Regulates Multiple Downstream Pathways;68
9.6.4;Front and Back Signaling;69
9.6.5;Mechanisms of Directional Sensing;71
9.6.6;Polarization;72
9.6.7;Conclusion;73
9.6.8;Acknowledgements;73
9.6.9;References;73
9.7;Chapter 8: Interactive Signaling Pathways in the Vasculature;76
9.7.1;Introduction;76
9.7.2;Interactive Networks as Models of Cell Signaling;76
9.7.3;Cross-Talk Between FGF and Notch Signaling;76
9.7.4;Novel Modulators of TGFß Signaling;78
9.7.5;Notch, FGF, and Smad Signaling Interactions;79
9.7.6;Feedback Inhibitory Mechanisms in Vascular Cell Signaling;79
9.7.7;Implications in Vascular Remodeling;80
9.7.8;References;80
9.8;Chapter 9: Signaling Pathways Involved in Cardiogenesis;84
9.8.1;Introduction;84
9.8.2;Origin of Cardiomyocyte Precursors;84
9.8.3;Cardiomyocyte and Heart Tube Formation;86
9.8.4;Complex Regulation of Cardiac Morphogenesis;87
9.8.5;Molecular Regulation of Septal Formation;89
9.8.6;Microrna Regulation of Cardiomyocyte Differentiation;89
9.8.7;Summary;90
9.8.8;Acknowledgements;90
9.8.9;References;90
9.9;Chapter 10: Calcium Signaling in Cardiac Muscle;94
9.9.1;Introduction;94
9.9.2;Calcium-Induced Calcium Release;94
9.9.3;How is SR Calcium Content Controlled?;95
9.9.4;Which Factors Control the Amplitude of the Systolic Calcium Transient?;95
9.9.5;Calcium Signaling in Heart Failure;96
9.9.6;References;96
9.10;Chapter 11: Calcium Signaling in Smooth Muscle;98
9.10.1;Introduction;98
9.10.2;The Role of Calcium Signaling in Smooth Muscle;98
9.10.3;Overview of Types of Calcium Signals in Smooth Muscle;99
9.10.4;Calcium Entry Mechanisms;100
9.10.5;Calcium Efflux Mechanisms;101
9.10.6;SR and Calcium Signaling;101
9.10.7;Mitochondrial and Other Organellar Contribution to Calcium Signaling;105
9.10.8;Global Calcium Transients;105
9.10.9;Local Calcium Signals;105
9.10.10;Calcium Oscillations and Waves;106
9.10.11;Caveolae, Microdomains, and Calcium Signals;107
9.10.12;References;108
9.11;Chapter 12: Trophic Effects of Gut Hormones in the Gastrointestinal Tract;116
9.11.1;Introduction;116
9.11.2;Trophic Effects of Gut Peptides in the Stomach, Small Bowel, and Colon;116
9.11.3;GI Hormone Receptors and Signal Transduction Pathways;118
9.11.4;Signaling Pathways Mediating the Effects of Intestinal Peptides;119
9.11.5;Conclusions;121
9.11.6;Acknowledgements;121
9.11.7;References;121
9.12;Chapter 13: Cell – Cell and Cell – Matrix Interactions in Bone;126
9.12.1;Introduction to Bone and Bone Disease;126
9.12.2;Diseases of Bone;126
9.12.3;Bone Cells and their Functions;127
9.12.4;Mechanical Strain;128
9.12.5;Hormones Responsible for Bone Development, Growth and Maintenance;129
9.12.6;Growth, Signaling, and Transcription Factors Responsible for Bone Development and Growth;131
9.12.7;Bone Extracellular Matrix (ECM);135
9.12.8;Conclusion anSummary;136
9.12.9;References;136
9.13;Chapter 14: Cell – Cell Signaling in the Testis and Ovary;142
9.13.1;Introduction;142
9.13.2;Cell – Cell Signaling in the Testis;142
9.13.3;Cell – Cell Signaling in the Ovary;146
9.13.4;Summary;150
9.13.5;References;150
9.14;Chapter 15: Kidney;158
9.14.1;Overview of Kidney Function and Cell-to-Cell Interactions;158
9.14.2;Vascular Smooth Muscle Cells;160
9.14.3;Vascular Endothelial Cells;161
9.14.4;Vasoactive Paracrine/Autocrine Agents – Actions in the Renal Vasculature;164
9.14.5;Endothelial Cell Connections: Connexins and Gap Junctions;168
9.14.6;Paracrine Signaling in Renal-Tubule Epithelial Cells;172
9.14.7;Interstitial Cell – Tubule Communication;177
9.14.8;Conclusions;178
9.14.9;Acknowledgements;179
9.14.10;References;179
9.15;Chapter16: Cytokines and Cytokine Receptors Regulating Cell Survival, Proliferation, and Differentiation in Hematopoiesis;184
9.15.1;General Aspects of Hematopoiesis;184
9.15.2;Hematopoietic Cytokines;184
9.15.3;Signaling through Cytokine Receptors;186
9.15.4;Concluding Statements;193
9.15.5;References;193
9.16;Chapter 17: CD45;194
9.16.1;Introduction;194
9.16.2;Structure;194
9.16.3;Function;195
9.16.4;Regulation;196
9.16.5;Synopsis;197
9.16.6;Acknowledgements;197
9.16.7;References;198
9.17;Chapter 18: Signal Transduction in T Lymphocytes;200
9.17.1;Introduction;200
9.17.2;Signaling Receptors in T Cells form Dynamic Macromolecular Signaling Complexes;207
9.17.3;Co-receptor and Co-stimulatory Proteins Modulate T Cell Signaling Pathways ;203
9.17.4;Intracellular Signaling Pathways Induced by Antigen Stimulation of T Cells;206
9.17.5;Conclusions;207
9.17.6;References;207
9.18;Chapter 19: Signal Transduction via the B Cell Antigen Receptor: A Crucial Regulator of B Cell Biology;210
9.18.1;Introduction;210
9.18.2;Initiation of Signal Transduction through the BCR;210
9.18.3;Propagation of Signal Transduction Via the BCR;211
9.18.4;Conclusion;216
9.18.5;References;216
9.19;Chapter 20: Signaling Pathways Regulating Growth and Differentiation of Adult Stem Cells;220
9.19.1;Introduction;220
9.19.2;Stem Cell Properties;220
9.19.3;Signaling Intermediates and Pathways in CD133 Stem Cells;221
9.19.4;Conclusions;226
9.19.5;References;226
10;Section C: Signaling in Development;230
10.1;Chapter 21: Wnt Signaling in Development;232
10.1.1;Introduction;232
10.1.2;Canonical Wnt Signaling;232
10.1.3;Wnt Signaling in Invertebrate Development;232
10.1.4;Wnt Signaling in Vertebrate Development;233
10.1.5;Wnt/Planar Cell Polarity;234
10.1.6;Acknowledgements;235
10.1.7;References;235
10.2;Chapter 22: Interactions between Wnt/ß -Catenin/Fgf and Chemokine Signaling in Lateral Line Morphogenesis;238
10.2.1;Introduction;238
10.2.2;FGF Signaling Controls Sensory Organ Formation in the Migrating Primordium;239
10.2.3;Wnt/ß -Catenin Signaling Restricts Neurogenesis to Trailing Cells and Maintains the Progenitor Zone;240
10.2.4;The FGF Pathway Restricts Wnt/ß - Catenin Signaling to the Leading Edge Ensuring Normal Migration;240
10.2.5;Chemokine Signaling Guides the Migrating Primordium;241
10.2.6;A Feedback Loop Between FGF and Wnt/ß -Catenin Signaling Controls Migration by Localizing Chemokine Receptor Expression;242
10.2.7;Cell Migration and Rosettogenesis are Independently Regulated;242
10.2.8;Summary;242
10.2.9;References;242
10.3;Chapter 23: Integration of BMP, RTK, and Wnt Signaling Through Smad1 Phosphorylations;244
10.3.1;Introduction;244
10.3.2;Neural Induction: Linking RTKs and Anti-BMP Signals;244
10.3.3;MAPK Activation Explains Heterologous Neural Inducers;245
10.3.4;Epidermal Differentiation: Integration of Wnt and BMP Signals;245
10.3.5;Smad1 as a Platform for MAPK Integration;246
10.3.6;Smad1 as a Platform for Wnt Signals;246
10.3.7;A Conserved Mechanism of Signal Integration;247
10.3.8;Concluding Remarks;247
10.3.9;References;247
10.4;Chapter 24: Hedgehog Signaling in Development and Disease;250
10.4.1;The Hedgehog Proteins: Generation and Distribution;250
10.4.2;Transmitting the HH Signal;250
10.4.3;HH in Development and Disease;251
10.4.4;Acknowledgements;253
10.4.5;References;253
10.5;Chapter 25: Regulation of Vertebrate Left-Right Axis Development by Calcium;256
10.5.1;Introduction;256
10.5.2;Conserved Molecular Pathways Regulating LR Asymmetry;256
10.5.3;Initiating a Break in Symmetry;257
10.5.4;Conserved Role of Calcium in Left – Right Asymmetry Determination;258
10.5.5;Conclusions;259
10.5.6;Acknowledgements;260
10.5.7;References;260
10.6;Chapter 26: LIN-12/Notch Signaling: Induction, Lateral Specification, and Interaction with the EGF/Ras Pathway;262
10.6.1;The LIN-12/Notch Pathway;262
10.6.2;Inductive Signaling Versus Lateral Specification;262
10.6.3;Cellular outcome of the Activation of the LIN-12/Notch Pathway;265
10.6.4;Acknowledgement;265
10.6.5;References;266
10.7;Chapter 27: Proteolytic Activation of Notch Signaling: Roles for Ligand Endocytosis and Mechanotransduction;268
10.7.1;Introduction;268
10.7.2;DSL Ligand Endocytosis is Required for Activation of Notch Signaling;269
10.7.3;Ubiquitin and Epsin-Dependent Recycling to Produce an Active DSL Ligand;269
10.7.4;Notch Signaling Requires Proteolysis and Nuclear Translocation;270
10.7.5;DSL Ligand Endocytosis to Produce a Force for Notch Proteolytic Activation;270
10.7.6;Converting DSL Ligand Endocytosis into a Force-Generating Process;271
10.7.7;Conclusions and Future Directions;272
10.7.8;References;272
10.8;Chapter 28:Vascular Endothelial Growth Factors and Receptors: Signaling in Vascular Development;276
10.8.1;Introduction to Vegfs and VEGF Receptors;276
10.8.2;Developmental Processes; Vasculogenesis and Angiogenesis;277
10.8.3;VEGFR2 and its Ligands in Vascular Development ;277
10.8.4;VEGFR1 and its Ligands in Vascular Development and Inflammatory Responses ;281
10.8.5;VEGFR3 and its Ligands in Lymphatic Development ;281
10.8.6;VEGF and its Coreceptors in Modulation of Signal Transduction ;282
10.8.7;Conclusions;283
10.8.8;Acknowledgements;283
10.8.9;References;283
10.9;Chapter 29:BMPs in Development;288
10.9.1;Introduction;288
10.9.2;BMP Signal Transduction;288
10.9.3;Extracellular and Intracellular BMP Antagonists and the Establishment of Morphogen Gradients;290
10.9.4;Bmps in Vertebrate Embryo Patterning;291
10.9.5;Bmps and Bone Development;291
10.9.6;Perspectives;292
10.9.7;References;292
10.10;Chapter 30: Signaling from Fibroblast Growth Factor Receptors in Development and Disease;296
10.10.1;Introduction;296
10.10.2;FGFR Expression and Role During Development;296
10.10.3;Signaling Pathways Mediated by FGFRs;297
10.10.4;FGFRs and Developmental Disorders ;297
10.10.5;Role of FGFRs in Human Cancer;298
10.10.6;References;300
10.11;Chapter 31: Regulation of Synaptic Fusion by Heterotrimeric G Proteins;306
10.11.1;Introduction;306
10.11.2;The Vesicle Fusion Machinery;306
10.11.3;Modes of Synaptic Vesicle Fusion;307
10.11.4;G-Protein-Coupled Receptor Mediated Modulation at the Presynaptic Terminal;307
10.11.5;Possible Mechanisms of Presynaptic Inhibition by G Proteins;307
10.11.6;GaQ Signaling Ca2+ Stores, Dag and Modulation of Neurotransmitter Release ;310
10.11.7;G Proteins and Phosphorylation;310
10.11.8;References;310
10.12;Chapter 32: The Role of Receptor Protein Tyrosine Phosphatases in Axonal Pathfinding;314
10.12.1;Introduction;314
10.12.2;RPTPS and the Visual System;314
10.12.3;Neuromuscular System;316
10.12.4;Further Axon Growth and Guidance Roles;316
10.12.5;Axonal Signaling by RPTPS.;316
10.12.6;References;318
10.13;Chapter: 33 Neurotrophin Signaling in Development;320
10.13.1;Introduction;320
10.13.2;The Neurotrophin Ligands;320
10.13.3;Neurotrophin Receptors;321
10.13.4;Signaling Specificity During Development;321
10.13.5;Interacting Proteins;322
10.13.6;Retrograde Axonal Transport;323
10.13.7;Neurotrophin Signaling in the Adult Nervous System;323
10.13.8;References;323
10.14;Chapter: 34 Attractive and Repulsive Signaling in Nerve Growth Cone Navigation;326
10.14.1;Introduction;326
10.14.2;Netrin Signaling;326
10.14.3;Semaphorin Signaling;327
10.14.4;Slit Signaling;328
10.14.5;Ephrin Signaling;328
10.14.6;Nogo and Myelin-Associated Glycoprotein Signaling;328
10.14.7;Critical Roles of Modulatory Signals;328
10.14.8;Concluding Remarks;329
10.14.9;References;329
10.15;Chapter 35: Semaphorins and their Receptors in Vertebrates and Invertebrates;332
10.15.1;The Semaphorin Family;332
10.15.2;Receptors for Semaphorins;332
10.15.3;Intracellular Signaling Pathways;333
10.15.4;CRMP;333
10.15.5;Summary and Future Directions;334
10.15.6;Acknowledgements;335
10.15.7;References;335
10.16;Chapter 36: Signaling Pathways that Regulate Cell Fate in the Embryonic Spinal Cord;338
10.16.1;Introduction;338
10.16.2;Patterning Along the Dorsoventral Axis;338
10.16.3;Dorsal Spinal Cord Development;338
10.16.4;Ventral Spinal Cord Development;342
10.16.5;Rostrocaudal Specification;343
10.16.6;References;344
11;Section D: Signaling in Disease;346
11.1;Chapter 37: Ras and Cancer;348
11.1.1;Introduction: Ras Activation in Cancer;348
11.1.2;Pathways Downstream of Ras;348
11.1.3;Mouse Models of Cancer;349
11.1.4;Prospects for Cancer Therapy Based on Ras;350
11.1.5;References;350
11.2;Chapter 38: Targeting Ras for Anticancer Drug Discovery;352
11.2.1;Introduction;352
11.2.2;Ras Proteins Function as Signaling Nodes;352
11.2.3;Ras Activation in Human Cancers: Validation and Druggability;353
11.2.4;Targeting Ras Membrane Association;354
11.2.5;Targeting Ras Effector Signaling;360
11.2.6;Inhibitors of PI3K-AKT-MTOR Signaling;363
11.2.7;Inhibitors of Other Ras Effector Pathways;366
11.2.8;Conclusions and Future Directions;367
11.2.9;Acknowledgements;367
11.2.10;References;367
11.3;Chapter 39: The Roles of Ras Family Small GTPases in Breast Cancer;374
11.3.1;Introduction;374
11.3.2;Ras in Breast Cancer;376
11.3.3;Rheb;377
11.3.4;ARHI/DI-Ras3/NOEY2;378
11.3.5;Rerg;379
11.3.6;Therapeutic Re-Expression of ARHI or Rerg in Breast Cancer;379
11.3.7;Other Ras Family Proteins in Breast Cancer;380
11.3.8;References;380
11.4;Chapter 40: Signaling Pathways in the Normal and Neoplastic Breast;384
11.4.1;Introduction;384
11.4.2;The Epidermal Growth Factor Family;385
11.4.3;Other Growth Factor Families;387
11.4.4;The PI 3-Kinase – AKT and PTEN Axis;387
11.4.5;Conclusions;388
11.4.6;Acknowledgements;389
11.4.7;Dedication;389
11.4.8;References;389
11.5;Chapter 41: Aberrant Signaling Pathways in Pancreatic Cancer: Opportunities for Targeted Therapeutics;392
11.5.1;Introduction;392
11.5.2;Oncogenic Activation in PDAC;393
11.5.3;Loss of Tumor Suppressor Function in PDAC;395
11.5.4;Contributions of Pancreatic Stroma and Stromal Components in PDAC;396
11.5.5;Differentiation;397
11.5.6;Apoptotic Pathways and Apoptotic Resistance;398
11.5.7;Clinical Aspects of PDAC;398
11.5.8;Conclusions;400
11.5.9;Acknowledgement;400
11.5.10;References;400
11.6;Chapter 42: Regulatory Signaling in Pancreatic Organogenesis: Implications for Aberrant Signaling in Pancreatic Cancer;408
11.6.1;Introduction;408
11.6.2;Notch Signaling Pathway;408
11.6.3;Hedgehog Signaling Pathway;409
11.6.4;Transforming Growth Factor-Beta Signaling Pathway;410
11.6.5;Wnt Signaling Pathway;412
11.6.6;Fibroblast Growth Factors Signaling Pathway;412
11.6.7;Conclusion;414
11.6.8;Acknowledgements;414
11.6.9;References;414
11.7;Chapter 43: Angiogenesis Signaling Pathways as Targets in Cancer Therapy;418
11.7.1;Introduction;418
11.7.2;Overview of Angiogenesis and its Role in Tumor Development;418
11.7.3;Tumor Vessel Structure;418
11.7.4;Tumor Stroma and the Extracellular Matrix;419
11.7.5;The Role of Hypoxia in Regulating Tumor Angiogenesis;419
11.7.6;Overview of Critical Pathways Involved in Stimulating Angiogenesis;420
11.7.7;The Role of Cytokines in Angiogenesis;421
11.7.8;The Angiopoietins and the Angiogenic Shift;422
11.7.9;Angiogenesis Inhibitors;422
11.7.10;Anti-Angiogenesis Approaches and Treatments;423
11.7.11;Implications of Targeting Angiogenesis – Advantages And Disadvantages;424
11.7.12;Conclusions;424
11.7.13;Acknowledgement;424
11.7.14;References;424
11.8;Chapter 44: Clinical Applications of Kinase Inhibitors in Solid Tumors;430
11.8.1;Introduction;430
11.8.2;Rationale for Kinase Inhibition in the Treatment of Solid Tumors;430
11.8.3;Kinase Inhibition in Gastrointestinal Stromal Tumors;432
11.8.4;Kinase Inhibitors in Non-Small Cell Lung Cancer;434
11.8.5;EGFR Mutations in Lung Cancer;436
11.8.6;Kinase Inhibitors in Renal Cell Carcinoma;438
11.8.7;Kinase Inhibitors in Other Solid Tumors;440
11.8.8;Lessons Learned?;440
11.8.9;Glossary;441
11.8.10;Acknowledgements;441
11.8.11;References;441
11.9;Chapter 45: Adipokine Signaling: Implications for Obesity;448
11.9.1;Adipose Tissue and its Relation to Obesity;448
11.9.2;Leptin;448
11.9.3;Adiponectin;452
11.9.4;Proinflammatory Cytokines;453
11.9.5;Other Adipokines Related to Obesity;454
11.9.6;Concluding Remarks;454
11.9.7;Acknowledgement;454
11.9.8;References;454
11.10;Chapter 46: CXC Chemokine Signaling in Interstitial Lung Diseases;458
11.10.1;Introduction;458
11.10.2;Chemokine Regulation of Angiogenesis in Pulmonary Fibrosis: Reciprocal Roles of CXCR2 and CXCR3;458
11.10.3;Mesenchymal Progenitors in Pulmonary Fibrosis: Role of CXCR4;459
11.10.4;Potential Therapeutic Applications of Chemokine Signaling;460
11.10.5;Conclusions;460
11.10.6;Acknowledgement;460
11.10.7;References;460
11.11;Chapter 47: ER and Oxidative Stress: Implications in Disease;464
11.11.1;Introduction;464
11.11.2;UPR Signaling;464
11.11.3;IRE1 Signaling;465
11.11.4;PERK Signaling;466
11.11.5;ATF6 Signaling;466
11.11.6;ER Stress Induced Apoptosis;467
11.11.7;ER – Mitochondrial Interactions;468
11.11.8;Oxidative Protein Folding in the ER;468
11.11.9;ER Stress and Oxidative Stress: Implications in Human Disease;468
11.11.10;UPR and Oxidative Stress in Metabolic Disease;469
11.11.11;Neurodegenerative Diseases;469
11.11.12;Future Directions;470
11.11.13;Acknowledgements;470
11.11.14;References;470
11.12;Chapter 48: Protein Serine/Threonine Phosphatase Inhibitors and Human Disease;474
11.12.1;Introduction;474
11.12.2;Environmental Toxins as Phosphatase Inhibitors;474
11.12.3;New Insights in Cellular Phosphatase Inhibitors;475
11.12.4;Cellular Phosphatase Inhibitors and Human Disease;476
11.12.5;Concluding Remarks;477
11.12.6;References;478
11.13;Chapter 49: Signal Transduction in Rheumatoid Arthritis and Systemic Lupus Erythematosus;480
11.13.1;Introduction;480
11.13.2;STAT4 RS7574865 Allele and the Risk of RA;481
11.13.3;TNFR1 and C5 (RS376147 and RS2900180) and the Risk of RA;481
11.13.4;Challenges to the Application of Findings from Genetic Mapping Studies to Clinical Consequences;482
11.13.5;PTPN22;483
11.13.6;CTLA4;484
11.13.7;IL4R Variants I50V and Q551R and RA;484
11.13.8;TLR Signaling and Arthritis and Autoimmunity;484
11.13.9;NF.B Signaling in Arthritis and Inflammation;485
11.13.10;B Cell Signaling in Autoimmunity;485
11.13.11;CD22;488
11.13.12;PD-1;489
11.13.13;SHP-1;489
11.13.14;Ship;490
11.13.15;Summary;490
11.13.16;References;490
11.14;Chapter 50: Translational Concepts in Vasculitis;494
11.14.1;Introduction;494
11.14.2;Mechanisms in the Pathogenesis of Vasculitis;494
11.14.3;Translational Approaches to Therapeutics in Vasculitis;499
11.14.4;Classification Of Vasculitic Syndromes;500
11.14.5;Conclusions;501
11.14.6;References;502
11.15;Chapter 51: Translational Implications of Proteomics;506
11.15.1;Introduction;506
11.15.2;Profiling of Tissues to Identify Potential Circulating Markers;506
11.15.3;Proteomic Profiling of Proximal Biological Fluids;507
11.15.4;Profiling of Tumor Cell Populations;507
11.15.5;Profiling the Plasma Proteome for Cancer Biomarker Identification;507
11.15.6;Posttranslational Modifications as A Source of Cancer Biomarkers;509
11.15.7;Microarray Based Approaches for Biomarker Identification;510
11.15.8;Validation Strategies for Discovered Protein Biomarkers;510
11.15.9;References;510
11.16;Chapter 52: Translational Implications of MicroRNAs in Clinical Diagnostics and Therapeutics;512
11.16.1;Biogenesis and Functions of Animal Micrornas;512
11.16.2;Micrornas in Physiological and Metabolic Processes;514
11.16.3;Micrornas in Human Disease;516
11.16.4;Micrornas in Human Cancer;516
11.16.5;Micrornas and Viral Life Cycles;520
11.16.6;Future Microrna Based Therapeutic Strategies;520
11.16.7;Conclusions;524
11.16.8;Acknowledgements;524
11.16.9;References;524
12;Index;530