Biochemistry of Signal Transduction and Regulation

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).

• Preface xxvii1 Basics of Cell Signaling 11.1 Cell Signaling: Why, When, and Where? 11.2 Intercellular Signaling 31.3 Hormones in Intercellular Signaling 81.4 Intracellular Signaling: Basics 151.5 Molecular Tools for Intracellular Signaling 182 Structural Properties, Regulation and Posttranslational Modification of Signaling Proteins 272.1 Modular Structure of Signaling Proteins 272.2 Modular Signaling Complexes 312.3 Regulation of Signaling Enzymes by Effector Binding 342.4 Posttranslational Modifications (PTMs) in Cellular Signaling 362.5 Regulation by Protein Phosphorylation 512.6 Regulation by Protein Lysine Acetylation 552.7 Regulation by Protein Methylation 582.8 Ubiquitin Modification of Proteins 622.9 Lipidation of Signaling Proteins 90Questions 99References 1003 Organization of Signaling 1033.1 Scaffold Proteins 1033.2 Signal Processing in Signaling Paths and Signaling Networks 1083.3 Architecture of Signaling Pathways 113Questions 127References 1274 The Regulation of Gene Expression 1294.1 The Basic Steps of Gene Expression 1294.2 The Components of the Eukaryotic Transcription Machinery 1314.3 The Principles of Transcription Regulation 1494.4 The Control of Transcription Factors 1654.5 Chromatin Structure and Transcription Regulation 175Questions 205References 2065 RNA Processing, Translational Regulation, and RNA Interference 2095.1 Pre-mRNA Processing 2095.2 Regulation at the Level of Translation 2175.3 Regulation by RNA Silencing 229Questions 247References 2486 Signaling by Nuclear Receptors 2516.1 Ligands of Nuclear Receptors (NRs) 2526.2 Principles of Signaling by Nuclear Receptors (NRs) 2546.3 Structure of Nuclear Receptors (NRs) 2576.4 Transcriptional Regulation by NRs 2686.5 Regulation of Signaling by Nuclear Receptors 2746.6 Subcellular Localization of NRs 2806.7 Nongenomic Functions of NRs and their Ligands 284Questions 289References 2897 G Protein-Coupled Signal Transmission Pathways 2917.1 Transmembrane Receptors: General Structure and Classification 2917.2 Structural Principles of Transmembrane Receptors 2947.3 G Protein-Coupled Receptors 3017.4 Regulatory GTPases 3207.5 The Heterotrimeric G Proteins 3277.6 Receptor-independent Functions of Heterotrimeric G Proteins 3507.7 Effector Molecules of G Proteins 3527.8 GPCR Signaling via Arrestin 363Questions 365References 3668 Intracellular Messenger Substances: “Second Messengers” 3698.1 General Properties of Intracellular Messenger Substances 3698.2 Cyclic AMP 3718.3 cGMP and Guanylyl Cyclases 3758.4 Metabolism of Inositol Phospholipids and Inositol Phosphates 3788.5 Storage and Release of Ca2= 3838.6 Functions of Phosphoinositides 3928.7 Ca2+ as a Signal Molecule 3948.8 Diacylglycerol as a Signal Molecule 4018.9 Other Lipid Messengers: Ceramide, Sphingosine, and Lysophosphatidic Acid 4018.10 The NO Signaling Molecule 404Questions 414References 4159 Ser/Thr-Specific Protein Kinases and Protein Phosphatases 4179.1 Classification, Structure, and Characteristics of Protein Kinases 4179.2 Structure and Regulation of Protein Kinases 4209.3 Protein Kinase A 4319.4 The PI3 Kinase/Akt Pathway 4399.5 Protein Kinase C 4479.6 Ca2+/Calmodulin-Dependent Protein Kinases, CaM Kinases 4559.7 Ser/Thr-Specific Protein Phosphatases 461Questions 469References 47010 Signal Transmission via Transmembrane Receptors with Tyrosine-Specific Protein Kinase Activity 47310.1 Structure and Function of RTKs 47410.2 Downstream Effector Proteins of RTKs 49410.3 Nonreceptor Tyrosine-Specific Protein Kinases, Non-RTKs 50710.4 Protein Tyrosine Phosphatases 519Questions 532References 53311 Signal Transmission via Ras Proteins 53511.1 The Ras Superfamily of Monomeric GTPases 53511.2 GTPase-Activating Proteins (GAPs) of the Monomeric GTPases 53911.3 Guanine Nucleotide Exchange Factors (GEFs) of the Monomeric GTPases 54111.4 Guanine Nucleotide Dissociation Inhibitors (GDIs) 54411.5 The Ras Family of Monomeric GTPases 54511.6 Raf Kinase as an Effector of Signal Transduction by Ras Proteins 55511.7 Further Ras Family Members: R-Ras, Ral, and Rap 56111.8 Reception and Transmission of Multiple Signals by Ras Protein 56211.9 The Further Branches of the Ras Superfamily 568Questions 570References 57112 Intracellular Signal Transduction: The MAP Kinase Pathways 57312.1 Organization and Components of MAPK Pathways 57512.2 Regulation of MAPK Pathways by Protein Phosphatases and Inhibitor Proteins 57912.3 Scaffolding in MAPK Signaling 58312.4 The Major MAPK Pathways of Mammals 586Questions 592References 59213 Membrane Receptors with Associated Tyrosine Kinase Activity 59313.1 Cytokines and Cytokine Receptors 59313.2 The Jak-STAT Pathway 60813.3 T- and B-Cell Receptors 61813.4 Signal Transduction via Integrins 623Questions 628References 62914 Other Transmembrane Receptor Classes: Signaling by TGF-β Receptors, TNF Receptors, Toll Receptors, and Notch 63114.1 Receptors with Intrinsic Ser/Thr Kinase Activity: The TGF-β Receptor and Smad Protein Signaling 63114.2 Receptor Regulation by Intramembrane Proteolysis: The Notch Receptor 64214.3 Tumor Necrosis Factor Receptor (TNFR) Superfamily 64814.4 Toll-Like Receptor Signaling 653Questions 658References 65915 Cell-Cycle Control by External Signaling Pathways 66115.1 Principles of Cell-Cycle Control 66115.2 Key Elements of the Cell-Cycle Apparatus 66615.3 Regulation of the Cell Cycle by Proteolysis 68115.4 G 1 Progression and S Phase Entry 68415.5 Transit Through S Phase and M Phase 69915.6 DNA Damage and DNA Replication Checkpoints 702Questions 712References 71316 Malfunction of Signaling Pathways and Tumorigenesis: Oncogenes and Tumor Suppressor Genes 71516.1 Basic Characteristics of Tumor Cells 71516.2 Mutations in Cancer Cells 71516.3 Common Physiologic Changes in Tumor Cells: The Hallmarks of Cancer 72516.4 Signaling Proteins Mutated in Cancer: Oncogenes 72916.5 Tumor Suppressor Genes: General Functions 74116.6 Tumor Suppressors: Rb and ARF Proteins 74316.7 Tumor Suppressor Protein p 53 74716.8 Wnt/β-Catenin Signaling and the Tumor Suppressor APC 770Questions 773References 77417 Apoptosis 77717.1 Overview of Apoptotic Pathways 77817.2 Caspases: Death by Proteolysis 77917.3 The Family of Bcl-2 Proteins: Gatekeepers of Apoptosis 78617.4 The Mitochondrial Pathway of Apoptosis 78917.5 Death Receptor-Triggered Apoptosis 79217.6 Links of Apoptosis to Cellular Signaling Pathways 795Questions 799References 799Index 801