Signal transduction / Bastien D. Gomperts, Peter E.R. Tatham, Ijsbrand M. Kramer.

Format:

Book

Author/Creator:

Gomperts, B. D.

Contributor:

Kramer, Ijsbrand M.

Tatham, Peter E. R. (Life scientist)

Language:

English

Subjects (All):

Cellular signal transduction.

Signal Transduction.

Medical Subjects:

Signal Transduction.

Physical Description:

xiv, 424 pages : illustrations (some color) ; 26 cm

Place of Publication:

San Diego, Calif. : Academic Press, 2002.

Summary:

Signal Transduction is a text reference on cellular signalling processes. Starting with the basics, it explains how cells respond to external cues (hormones, cytokines, neurotransmitters, adhesion molecules, extracellular matrix etc), and shows how these inputs are integrated and co-ordinated. The first half of the book provides the conceptual framework, explaining the formation and action of second messengers, particularly cyclic nucleotides and calcium, and the mediation of signal pathways by GTP-binding proteins. The remaining chapters deal with the formation of complex signalling cascades employed by cytokines and adhesion molecules, starting at the membrane and ending in the nucleus, there to regulate gene transcription. In this context, growth is an important potential outcome and this has relevance to the cellular transformations that underlie cancer. The book ends with a description at the molecular level of how signalling proteins interact with their environment and with each other through their structural domains. Each main topic is introduced with a historical essay, detailing the sources, key observations and experiments that set the scene for recent and current work.

Contents:

1 Prologue: Signal transduction, origins and personalities 1

Transduction, the word and its meaning: one dictionary, different points of view 1

Hormones, evolution and history 2

Neurotransmitters 10

Ergot 12

Receptors and ligands 14

2 First messengers 19

Hormones 19

Binding of ligands to receptors 25

3 Receptors 33

Adrenaline (again) 33

[alpha]- and [beta]-adrenergic receptors 34

Acetylcholine receptors 38

Ion channel-linked receptors 42

The 7TM superfamily of G-protein linked receptors 51

Receptor-ligand interaction and receptor activation 58

Transmitting signals into cells 62

Intracellular 7TM receptor domains and signal transmission 65

Adrenaline (yet again) 66

4 GTP-binding proteins and signal transduction 71

Nucleotides as metabolic regulators 71

GTP-binding proteins, G-proteins or GTPases 72

Ras proteins 85

Ras-GAPs 92

Essay: Activation of G-proteins without subunit dissociation 95

5 Effector enzymes coupled to GTP-binding proteins: Adenylyl cyclase and phospholipase C 107

Adenylyl cyclase 107

Phospholipase C 119

6 The regulation of visual transduction 127

Sensitivity of photoreceptors 127

Photoreceptor mechanisms 130

Adaptation: calcium acts as a negative regulator 135

Photo-excitation of rhodopsin 137

Switching off the mechanism 139

A note on phototransduction in invertebrates 141

7 Calcium and signal transduction 145

A new second messenger is discovered 145

Calcium and evolution 146

Distinguishing Ca[superscript 2+] and Mg[superscript 2+] 147

Free, bound and trapped Ca[superscript 2+] 148

Cytosol Ca[superscript 2+] is kept low 149

Detecting changes in cytosol Ca[superscript 2+] 150

Mechanisms that elevate cytosol Ca[superscript 2+] concentration 153

The pattern of cytosol Ca[superscript 2+] changes in single cells 162

Localization of intracellular second messengers 166

8 Calcium signalling 171

Calcium binding by proteins 171

Effects of elevated calcium 172

Paradigms of calcium signalling 181

9 Phosphorylation and dephosphorylation: Protein kinases A and C 189

Protein phosphorylation as a switch in cellular functioning 189

cAMP and the amplification of signals 191

Protein kinase A 192

Protein kinase A and the regulation of transcription 194

Protein kinase A and the activation of ERK 196

Actions of cAMP not mediated by PKA 197

Protein kinase C 198

The protein kinase C family 199

Structural domains and activation of protein kinase C 201

Multiple sources of DAG and other lipids to activate PKC 204

Differential localization of PKC isoforms 205

PKC anchoring proteins, STICKs, PICKs and RACKs 205

PKC and cell transformation 208

PKC and inflammation 212

10 Growth factors: Setting the framework 225

Viruses and tumours 225

The discovery of NGF ... and EGF 227

Platelet derived growth factor 230

Transforming growth factors 231

Problems with nomenclature 232

Essay: The cell cycle 232

Essay: Cancer and cell transformation 246

11 Signalling pathways operated by receptor protein tyrosine kinases 257

The tyrosine kinase family 257

Tyrosine kinase-containing receptors 259

Branching of the signalling pathway 265

A switch in receptor signalling: Activation of ERK by 7TM receptors 276

12 Signalling pathways operated by non-receptor protein tyrosine kinases 283

The non-receptor protein tyrosine kinase family 283

Interferons and their effects 290

Oncogenes, malignancy and signal transduction 292

Essay: Non-receptor protein tyrosine kinases and their activation 294

13 Phosphoinositide 3-kinases, protein kinase B and signalling through the insulin receptor 299

Insulin receptor signalling; it took some time to discover 299

PI 3-kinase 300

Insulin: The role of IRS, PI 3-kinase and PKB in the regulation of glycogen synthesis 306

Other processes mediated by the 3-phosphorylated inositol phospholipids 309

Multiple kinases and multiple phosphorylation sites, PDK1 as an integrator of multiple inputs 310

So, who did discover insulin? 310

14 Signal transduction to and from adhesion molecules 315

Adhesion molecules 315

Adhesion molecules and cell survival 325

Adhesion molecules and regulation of the cell cycle 328

Adhesion molecules as tumour suppressors 331

Essay: Apoptosis 335

15 Adhesion molecules and trafficking of leukocytes 345

Inflammation and its mediators 345

TNF[alpha] and regulation of adhesion molecule expression in endothelial cells 349

16 Signalling through receptor bound protein serine/threonine kinases 359

The TGF[beta] family of growth factors 359

Downstream signalling; Drosophila, Caenorhabditis and Smad 364

17 Protein dephosphorylation and protein phosphorylation 373

The importance of dephosphorylation 373

The role of PTPs in signal transduction 376

Negative regulation through dephosphorylation 378

Serine-threonine phosphatases 383

Classification of protein serine-threonine phosphatases 384

18 Protein domains and signal transduction 393

Structurally conserved protein modules 393

Domains that bind oligopeptide motifs 395

Domains that bind proteins and lipids 398

Polypeptide modules that bind Ca[superscript 2+] 401

Protein kinase domains 403.

Notes:

Includes bibliographical references and index.

ISBN:

0122896319

OCLC:

48752824