Preface
Notes
How to View Stereo Images of Molecular Structures
References
Abbreviations
Genes and Gene Products
Amino Acids
Chapter 1. Prologue: Signal Transduction, Origins, and Ancestors
Transduction, the Word and its Meaning: One Dictionary, Different Points of View
Hormones, Evolution, and History
Hormones: A Definition
Neurotransmitters
Receptors and ligands
References
Chapter 2. First Messengers
Hormones
Intracellular Messengers
References
Chapter 3. Receptors
Adrenaline (Again)
α-and β-Adrenergic Receptors
Acetylcholine Receptors
Cholinergic Receptor Subtypes
The 7TM Superfamily of G-Protein-Linked Receptors
Categories of 7TM Receptor
Receptor–Ligand Interaction and Receptor Activation
Transmitting Signals into Cells
Intracellular 7TM Receptor Domains and Signal Transmission
References
Chapter 4. GTP-binding Proteins and Signal Transduction
Nucleotides as Metabolic Regulators
G Proteins
α-Subunits
βγ-Subunits
The G Protein Receptor Kinase Family
Receptor Phosphorylation, Down-Regulation and Pathway switching
Receptor Mechanisms Obviating G Proteins
Monomeric GTP-Binding Proteins
RasGAPs
Essay: Activation of G Proteins Without Subunit Unit dissociation
References
Chapter 5. Effector Enzymes Coupled to GTP Binding Proteins: Adenylyl Cyclase and Phospholipase C
Adenylyl cyclase
Phospholipase C
References
Chapter 6. The Regulation of Visual Transduction and Olfaction
Phototransduction
Sensitivity of Photoreceptors
Photoreceptor Mechanisms
Adaptation: Calcium Acts as a Negative Regulator
Photo-excitation of Rhodopsin
Switching Off the Mechanism
Note on Phototransduction in Invertebrates
Olfaction
References
Chapter 7. Intracellular Calcium
A New Second Messenger is Discovered
Calcium and Evolution
Distinguishing Ca2+ and Mg2+
Free, Bound, and Trapped Ca2+
Cytosol Ca2+ is Kept Low
Extracellular Calcium and Activation
Sensing Changes in Intracellular Ca2+ Concentration
Mechanisms that Elevate Cytosol Ca2+ Concentration
Ca2+ Microdomains and Global Cellular Signals
References
Chapter 8. Calcium Effectors
Calcium-Binding by Proteins
Paradigms of Calcium Signalling
References
Chapter 9. Phosphorylation and Dephosphorylation: Protein Kinases A and C
Protein Phosphorylation as a Switch in Cellular Functioning
Cyclic AMP and the Amplification of Signals
Protein Kinase A
Protein Kinase A and the Regulation of Transcription
Protein Kinase A and the Activation Of ERK
Actions of cAMP not Mediated by PKA
Protein Kinase C
The Protein Kinase C Family
Structural Domains and Activation of Protein Kinase C
Activation of Protein Kinase C
References
Chapter 10. Nuclear Receptors
First Steps in the Isolation of Steroid Hormones
The Discovery of Intracellular Hormone Receptors
A Superfamily of Nuclear Receptors
Nomenclature of Nuclear Receptors
Receptor Structure and Ligand Binding
DNA Binding
Activation and Repression of Transcription
Interaction with Other Signalling Pathways
Non-Transcriptional Actions of Nuclear Receptors and Their Ligands
References
Chapter 11. Growth factors: Setting the Framework
Viruses and Tumours
The Discovery of NGF … and EGF
Platelet-Derived Growth Factor (PDGF)
Transforming Growth Factors (TGFα and TGFβ)
Problems with Nomenclature
Essay: Cancer and Transformation
References
Chapter 12. Signalling Pathways Operated by Receptor Protein Tyrosine Kinases
Introduction
Tyrosine Kinase-containing Receptors
Branching of the Signalling Pathway
Beyond ERK
Why are the Signalling Pathways so Complicated?
A Switch in Receptor Signalling: Activation of ERK by 7TM Receptors
References
Chapter 13. Signal Transduction to and from Adhesion Molecules
Adhesion Molecules
Integrins, Cell Survival, and Cell Proliferation
References
Chapter 14. Adhesion Molecules in the Regulation of Cell Differentiation: Mainly About Wnt
Destabilization of Adherens Junctions Causes Cellular De-Differentiation
Other Examples of Signalling Through Adhesion Molecules
References
Chapter 15. Activation of the Innate immune System: The Toll-like Receptor 4 and Signalling through Ubiquitylation
Essay: Ubiquitylation and SUMOylation
Essay: The Proteasome Complex
References
Chapter 16. Traffic of White Blood Cells
Inflammation and Leukocytes
References
Chapter 17. Tyrosine Protein Kinases and Adaptive Immunity: TCR, BCR, Soluble Tyrosine Kinases and NFAT
The Family of Non-Receptor Protein Tyrosine Kinases
T-Cell Receptor Signalling
Signalling Through Interferon Receptors
Oncogenes, Malignancy, and Signal Transduction
Essay: Non-Receptor Protein Tyrosine Kinases and Their Regulation
References
Chapter 18. Phosphoinositide 3-Kinases, Protein Kinase B, and Signalling through the Insulin Receptor
Insulin Receptor Signalling; It Took a Little Time to Work Out the Details
Signalling Through Phosphoinositides
PI 3-Kinase, PI(3,4)P2 and PI(3,4,5)P3
Insulin: The Role of IRS, PI 3-kinase, and PKB in the Regulation of Glycogen synthesis
Other Processes Mediated by the 3-Phosphorylated Inositol phospholipids
So, Who Did Discover Insulin?
References
Chapter 19. Protein Kinase C Revisited
PKC in Cell Transformation
Regulation of Cell Polarity
References
Chapter 20. Signalling Through Receptor Serine/Threonine Kinases
The TGFβ Family of Growth Factors
Downstream Signalling: Drosophila, Caenorhabitidis, and Smad
References
Chapter 21. Protein Dephosphorylation and Protein Phosphorylation
Protein Tyrosine Phosphatases
PTPs in Signal Transduction
Dual Specificity Phosphatases
Serine/Threonine Phosphatases
References
Chapter 22. Notch
Notched Wings, Morgan, and the Gene Theory
Membrane Components of the Notch Pathway
Notch and Sensory Progenitor Cells of Drosophila; the Importance of Endocytosis
References
Chapter 23. Targeting Transduction Pathways for Research and Medical Intervention
Chemotherapy
Alternative Targets for Cancer Therapy: Towards a Scientific Rationale
Inhibiting the EGF Family of Receptor Kinases
Other Signal Transduction Components Targeted for Therapeutic Intervention
Towards a Different Approach in Testing Cancer Drugs?
References
Chapter 24. Protein Domains and Signal Transduction
Modular Structure of Proteins
Structural Domains
The Evolution and Shuffling of Domains
Sequence Homology and the Acquisition of Function
The Inventory of Domains
Examples of Domains with Roles in Signalling
References
Index
