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Biochemistry of Signal Transduction and Regulation, 5th Edition

ISBN: 978-3-527-33366-0
844 pages
April 2014, ©2013
Biochemistry of Signal Transduction and Regulation, 5th Edition (3527333665) cover image

Description

Originally based on a graduate course taught by the author, this true classic has once again been extensively updated to incorporate key new findings in biological signaling. With over half of the content re-written, plus 70 brand new and 50 revised figures, this is the most up-to-date textbook on signaling available anywhere.

Thanks to its clear structure, hundreds of illustrative drawings, as well as chapter introductions and newly added study questions, this text excels as a companion for a course on biological signaling, and equally as an introductory reference to the field for students and researchers. Generations of students and junior researchers have relied on "the Krauss" to find their way through the bewildering complexity of biological signaling pathways.

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Table of Contents

Preface XXVII

1 Basics of Cell Signaling 1

1.1 Cell Signaling: Why, When, and Where? 1

1.2 Intercellular Signaling 3

1.3 Hormones in Intercellular Signaling 8

1.4 Intracellular Signaling: Basics 15

1.5 Molecular Tools for Intracellular Signaling 18

2 Structural Properties, Regulation and Posttranslational Modification of Signaling Proteins 27

2.1 Modular Structure of Signaling Proteins 27

2.2 Modular Signaling Complexes 31

2.3 Regulation of Signaling Enzymes by Effector Binding 34

2.4 Posttranslational Modifications (PTMs) in Cellular Signaling 36

2.5 Regulation by Protein Phosphorylation 51

2.6 Regulation by Protein Lysine Acetylation 55

2.7 Regulation by Protein Methylation 58

2.8 Ubiquitin Modification of Proteins 62

2.9 Lipidation of Signaling Proteins 90

3 Organization of Signaling 103

3.1 Scaffold Proteins 103

3.2 Signal Processing in Signaling Paths and Signaling Networks 108

3.3 Architecture of Signaling Pathways 113

4 The Regulation of Gene Expression 129

4.1 The Basic Steps of Gene Expression 129

4.2 The Components of the Eukaryotic Transcription Machinery 131

4.3 The Principles of Transcription Regulation 149

4.4 The Control of Transcription Factors 165

4.5 Chromatin Structure and Transcription Regulation 175

5 RNA Processing, Translational Regulation, and RNA Interference 209

5.1 Pre-mRNA Processing 209

5.2 Regulation at the Level of Translation 217

5.3 Regulation by RNA Silencing 229

6 Signaling by Nuclear Receptors 251

6.1 Ligands of Nuclear Receptors (NRs) 252

6.2 Principles of Signaling by Nuclear Receptors (NRs) 254

6.3 Structure of Nuclear Receptors (NRs) 257

6.4 Transcriptional Regulation by NRs 268

6.5 Regulation of Signaling by Nuclear Receptors 274

6.6 Subcellular Localization of NRs 280

6.7 Nongenomic Functions of NRs and their Ligands 284

7 G Protein-Coupled Signal Transmission Pathways 291

7.1 Transmembrane Receptors: General Structure and Classification 291

7.2 Structural Principles of Transmembrane Receptors 294

7.3 G Protein-Coupled Receptors 301

7.4 Regulatory GTPases 320

7.5 The Heterotrimeric G Proteins 327

7.6 Receptor-independent Functions of Heterotrimeric G Proteins 350

7.7 Effector Molecules of G Proteins 352

7.8 GPCR Signaling via Arrestin 363

8 Intracellular Messenger Substances: “Second Messengers” 369

8.1 General Properties of Intracellular Messenger Substances 369

8.2 Cyclic AMP 371

8.3 cGMP and Guanylyl Cyclases 375

8.4 Metabolism of Inositol Phospholipids and Inositol Phosphates 378

8.5 Storage and Release of Ca2þ 383

8.6 Functions of Phosphoinositides 392

8.7 Ca2þ as a Signal Molecule 394

8.8 Diacylglycerol as a Signal Molecule 401

8.9 Other Lipid Messengers: Ceramide, Sphingosine, and Lysophosphatidic Acid 401

8.10 The NO Signaling Molecule 404

9 Ser/Thr-Specific Protein Kinases and Protein Phosphatases 417

9.1 Classification, Structure, and Characteristics of Protein Kinases 417

9.2 Structure and Regulation of Protein Kinases 420

9.3 Protein Kinase A 431

9.4 The PI3 Kinase/Akt Pathway 439

9.5 Protein Kinase C 447

9.6 Ca2þ/Calmodulin-Dependent Protein Kinases, CaM Kinases 455

9.7 Ser/Thr-Specific Protein Phosphatases 461

10 Signal Transmission via Transmembrane Receptors with Tyrosine-Specific Protein Kinase Activity 473

10.1 Structure and Function of RTKs 474

10.2 Downstream Effector Proteins of RTKs 494

10.3 Nonreceptor Tyrosine-Specific Protein Kinases, Non-RTKs 507

10.4 Protein Tyrosine Phosphatases 519

11 Signal Transmission via Ras Proteins 535

11.1 The Ras Superfamily of Monomeric GTPases 535

11.2 GTPase-Activating Proteins (GAPs) of the Monomeric GTPases 539

11.3 Guanine Nucleotide Exchange Factors (GEFs) of the Monomeric GTPases 541

11.4 Guanine Nucleotide Dissociation Inhibitors (GDIs) 544

11.5 The Ras Family of Monomeric GTPases 545

11.6 Raf Kinase as an Effector of Signal Transduction by Ras Proteins 555

11.7 Further Ras Family Members: R-Ras, Ral, and Rap 561

11.8 Reception and Transmission of Multiple Signals by Ras Protein 562

11.9 The Further Branches of the Ras Superfamily 568

12 Intracellular Signal Transduction: The MAP Kinase Pathways 573

12.1 Organization and Components of MAPK Pathways 575

12.2 Regulation of MAPK Pathways by Protein Phosphatases and Inhibitor Proteins 579

12.3 Scaffolding in MAPK Signaling 583

12.4 The Major MAPK Pathways of Mammals 586

13 Membrane Receptors with Associated Tyrosine Kinase Activity 593

13.1 Cytokines and Cytokine Receptors 593

13.2 The Jak-STAT Pathway 608

13.3 T- and B-Cell Receptors 618

13.4 Signal Transduction via Integrins 623

14 Other Transmembrane Receptor Classes: Signaling by TGF-b Receptors, TNF Receptors, Toll Receptors, and Notch 631

14.1 Receptors with Intrinsic Ser/Thr Kinase Activity: The TGF-b Receptor and Smad Protein Signaling 631

14.2 Receptor Regulation by Intramembrane Proteolysis: The Notch Receptor 642

14.3 Tumor Necrosis Factor Receptor (TNFR) Superfamily 648

14.4 Toll-Like Receptor Signaling 653

15 Cell-Cycle Control by External Signaling Pathways 661

15.1 Principles of Cell-Cycle Control 661

15.2 Key Elements of the Cell-Cycle Apparatus 666

15.3 Regulation of the Cell Cycle by Proteolysis 681

15.4 G1 Progression and S Phase Entry 684

15.5 Transit Through S Phase and M Phase 699

15.6 DNA Damage and DNA Replication Checkpoints 702

16 Malfunction of Signaling Pathways and Tumorigenesis: Oncogenes and Tumor Suppressor Genes 715

16.1 Basic Characteristics of Tumor Cells 715

16.2 Mutations in Cancer Cells 715

16.3 Common Physiologic Changes in Tumor Cells: The Hallmarks of Cancer 725

16.4 Signaling Proteins Mutated in Cancer: Oncogenes 729

16.5 Tumor Suppressor Genes: General Functions 741

16.6 Tumor Suppressors: Rb and ARF Proteins 743

16.7 Tumor Suppressor Protein p53 747

16.8 Wnt/b-Catenin Signaling and the Tumor Suppressor APC 770

17 Apoptosis 777

17.1 Overview of Apoptotic Pathways 778

17.2 Caspases: Death by Proteolysis 779

17.3 The Family of Bcl-2 Proteins: Gatekeepers of Apoptosis 786

17.4 The Mitochondrial Pathway of Apoptosis 789

17.5 Death Receptor-Triggered Apoptosis 792

17.6 Links of Apoptosis to Cellular Signaling Pathways 795

Questions 799

References 799

Index 801

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Author Information

Gerhard Krauss is Professor of Biochemistry at the University of Bayreuth (Germany). His resarch is centered on the mechanism of interaction of DNA binding proteins and their target DNA. He is also a gifted teacher and textbook author, and for many years has been the head of the university education committee of the German Society of Biochemistry and Molecular Biology (GBM).
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