Signal Transduction (eBook)

Front Cover 1
Signal Transduction 6
Copyright Page 7
Contents 8
Preface 12
Chapter 1. Prologue: Signal transduction, origins and personalities 18
Transduction, the word and its meaning: one dictionary, different points of view 18
Hormones, evolution and history 19
Hormones: a definition 26
Neurotransmitters 27
Ergot 29
Receptors and ligands 31
Chapter 2. First messengers 36
Hormones 36
Binding of ligands to receptors 42
Chapter 3. Receptors 50
Adrenaline (again) 50
a- and ß-adrenergic receptors 51
Acetylcholine receptors 55
Ion channel-linked receptors 59
The 7TM superfamily of G-protein linked receptors 68
Receptor–ligand interaction and receptor activation 75
Transmitting signals into cells 79
Intracellular 7TM receptor domains and signal transmission 82
Adrenaline (yet again) 83
Chapter 4. GTP-binding proteins and signal transduction 88
Nucleotides as metabolic regulators 88
GTP-binding proteins, G-proteins or GTPases 89
Ras proteins 102
Ras-GAPs 109
Essay: Activation of G-proteins without subunit dissociation 112
Chapter 5. Effector enzymes coupled to GTP-binding proteins: Adenylyl cyclase and phospholipase C 124
Adenylyl cyclase 124
Phospholipase C 136
Chapter 6. The regulation of visual transduction 144
Sensitivity of photoreceptors 144
Photoreceptor mechanisms 147
Adaptation: calcium acts as a negative regulator 152
Photo-excitation of rhodopsin 154
Switching off the mechanism 156
A note on phototransduction in invertebrates 158
Chapter 7. Calcium and signal transduction 162
A new second messenger is discovered 162
Calcium and evolution 163
Distinguishing Ca2+ and Mg2+ 164
Free, bound and trapped Ca2+ 165
Cytosol Ca2+ is kept low 166
Detecting changes in cytosol Ca2+ 167
Mechanisms that elevate cytosol Ca2+ concentration 170
The pattern of cytosol Ca2+ changes in single cells 179
Localization of intracellular second messengers 183
Chapter 8. Calcium signalling 188
Calcium binding by proteins 188
Effects of elevated calcium 189
Paradigms of calcium signalling 198
Chapter 9. Phosphorylation and dephosphorylation: Protein kinases A and C 206
Protein phosphorylation as a switch in cellular functioning 206
cAMP and the amplification of signals 208
Protein kinase A 209
Protein kinase A and the regulation of transcription 211
Protein kinase A and the activation of ERK 213
Actions of cAMP not mediated by PKA 214
Protein kinase C 215
The protein kinase C family 216
Structural domains and activation of protein kinase C 218
Multiple sources of DAG and other lipids to activate PKC 221
Differential localization of PKC isoforms 222
PKC anchoring proteins, STICKs, PICKs and RACKs 222
PKC and cell transformation 225
PKC and inflammation 229
Chapter 10. Growth factors: Setting the framework 242
Viruses and tumours 242
The discovery of NGF... and EGF 244
Platelet derived growth factor 247
Transforming growth factors 248
Problems with nomenclature 249
Essay: The cell cycle 249
Essay: Cancer and cell transformation 263
Chapter 11. Signalling pathways operated by receptor protein tyrosine kinases 274
The tyrosine kinase family 274
Tyrosine kinase-containing receptors 276
Branching of the signalling pathway 282
A switch in receptor signalling: Activation of ERK by 7TM receptors 293
Chapter 12. Signalling pathways operated by non-receptor protein tyrosine kinases 300
The non-receptor protein tyrosine kinase family 300
Interferons and their effects 307
Oncogenes, malignancy and signal transduction 309
Essay: Non-receptor protein tyrosine kinases and their activation 311
Chapter 13. Phosphoinositide 3-kinases, protein kinase B and signalling through the insulin receptor 316
Insulin receptor signalling it took some time to discover
PI 3-kinase 317
Insulin: The role of IRS, PI 3-kinase and PKB in the regulation of glycogen synthesis 323
Other processes mediated by the 3-phosphorylated inositol phospholipids 326
Multiple kinases and multiple phosphorylation sites, PDK1 as an integrator of multiple inputs 327
So, who did discover insulin? 327
Chapter 14. Signal transduction to and from adhesion molecules 332
Adhesion molecules 332
Adhesion molecules and cell survival 342
Adhesion molecules and regulation of the cell cycle 345
Adhesion molecules as tumour suppressors 348
Essay: Apoptosis 352
Chapter 15. Adhesion molecules and trafficking of leukocytes 362
Inflammation and its mediators 362
TNFa and regulation of adhesion molecule expression in endothelial cells 366
Chapter 16. Signalling through receptor bound protein serine/threonine kinases 376
The TGFß family of growth factors 376
Downstream signalling Drosophila, Caenorhabditis and Smad
Chapter 17. Protein dephosphorylation and protein phosphorylation 390
The importance of dephosphorylation 390
The role of PTPs in signal transduction 393
Negative regulation through dephosphorylation 396
Serine-threonine phosphatases 400
Classification of protein serine-threonine phosphatases 402
Chapter 18. Protein domains and signal transduction 410
Structurally conserved protein modules 410
Domains that bind oligopeptide motifs 412
Domains that bind proteins and lipids 415
Polypeptide modules that bind Ca2+ 418
Protein kinase domains 420
Index 428