Cellular Signal Transduction in Toxicology and Pharmacology

Data Collection, Analysis, and Interpretation
Herausgegeben:Boyd, Jonathan W.; Neubig, Richard R.

• Gebundenes Buch

Produktbeschreibung

Covering a key topic due to growing research into the role of signaling mechanisms in toxicology, this book focuses on practical approaches for informatics, big data, and complex data sets.

_ Combines fundamentals / basics with experimental applications that can help those involved in preclinical drug studies and translational research
_ Includes detailed presentations of study methodology and data collection, analysis, and interpretation
_ Discusses tools like experimental design, sample handling, analytical measurement techniques

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Produktdetails

• Verlag: Wiley / Wiley & Sons
• Artikelnr. des Verlages: 1W119060260
• 1. Auflage
• Seitenzahl: 336
• Erscheinungstermin: 16. April 2019
• Englisch
• Abmessung: 231mm x 157mm x 23mm
• Gewicht: 680g
• ISBN-13: 9781119060260
• ISBN-10: 1119060265
• Artikelnr.: 44945570

Autorenporträt

JONATHAN W. BOYD, PHD, is an Associate Professor in the Department of Orthopaedics at West Virginia University School of Medicine. RICHARD R. NEUBIG, MD, PHD, is Chair and Professor in the Department of Pharmacology and Toxicology at Michigan State University.

Inhaltsangabe

List of Contributors xv

About the Editors xvii

Preface xix

1 Introduction to Cellular Signal Transduction: The Connection Between a Biological System and Its Surroundings 1
Jonathan W. Boyd, Richard R. Neubig, Alice Han, and Maren Prediger

1.1 Starting Big, but Ending Small 3

1.1.1 Key Features of Signal Transduction 3

1.2 Responding to Our Environment: Sensory Perception Begins and Ends with Signal Transduction 4

1.2.1 Taste (Gustation) 4

1.2.2 Smell (Olfaction) 5

1.2.3 Sight (Vision) 6

1.2.4 Sound (Audition) 6

1.2.5 Touch (Somatosensation) 8

1.3 Primary Transport Systems Involved in Signal Transduction 8

1.3.1 Ion Channels, Transporters, and Ion Pumps 9

1.3.2 Receptors 10

1.3.3 Endocytosis 10

1.3.4 Exosomes 11

1.4 Key Organelles Involved in Signal Transduction 12

1.4.1 Mitochondria 12

1.4.2 Endoplasmic Reticulum 14

1.4.3 Nucleus 15

References 16

2 Mechanisms of Cellular Signal Transduction 21
Richard R. Neubig, Jonathan W. Boyd, Julia A. Mouch, and Nicole Prince

2.1 Posttranslational Modifications and Their Roles in Signal Transduction 22

2.1.1 Phosphorylation 22

2.1.2 Acylation 24

2.1.3 Alkylation 25

2.1.4 Glycosylation 26

2.1.5 Other PTMs 27

2.2 Receptors 27

2.3 Receptor Signaling Mechanisms 29

2.3.1 Basic Principles of Signal Transduction Mechanisms 29

2.3.1.1 Selectivity and Recognition 31

2.3.1.2 Flexible Modularity 31

2.3.1.3 Molecular Switches 34

2.3.1.4 GPCRs and Second Messengers 36

2.3.1.5 Amplification 39

2.3.1.6 Turn-Off Mechanisms 40

2.3.1.7 Localization 40

2.3.1.8 Biased Signaling/Functional Selectivity 41

2.4 Receptor Tyrosine Kinases 42

2.5 Steroid Receptors 43

2.6 Reactive Oxygen Species (ROS) 43

2.7 Summary 44

References 44

3 From Cellular Mechanisms to Physiological Responses: Functional Signal Integration Across Multiple Biological Levels 49
Robert H. Newman

3.1 Introduction 49

3.2 Cellular Information Flow: Mechanisms of Cellular Signal Integration and Regulation 50

3.2.1 The InsR-aPKC-NF-kappaB Signaling Axis 51

3.2.2 Modes of Regulation in InsR-PKC-NF-kappaB Signaling Axis 54

3.2.3 Transcriptional Regulation 54

3.2.4 Regulating the Regulators: Phosphatase-Mediated Regulation of Signaling Molecules 59

3.3 Crosstalk and Functional Signal Integration in Response to Insulin in Hepatocytes 60

3.4 Systemic Signal Integration 65

3.4.1 Pancreatic ß-Cells 65

3.4.2 Skeletal Muscles 66

3.4.3 Adipose Tissue 67

3.5 Dysregulation of Insulin Signaling in the Etiology of Type 2

Diabetes 67

References 69

4 Signal Transduction in Disease: Relating Cell Signaling to Morbidity and Mortality 73
Patricia E. Ganey and Sean A. Misek

4.1 Introduction 73

4.2 Fibrosis as an Example of Complex Signaling 75

4.2.1 Development of Liver Fibrosis 75

4.2.2 Animal Models of Hepatic Fibrosis 76

4.2.3 Activation of Hepatic Stellate Cells 77

4.2.4 Epithelial-to-Mesenchymal Transition (EMT) 78

4.2.5 Other Cellular Interactions in Fibrosis 78

4.2.6 Intracellular Signaling Pathways Critical to Liver Fibrosis 80

4.2.6.1 TGF-ß1 80

4.2.6.2 Kinase Pathways Involved in Fibrotic Responses 82

4.2.6.3 HIF-1alpha 83

4.2.6