Main 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.

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 Ca2p 383 8.6 Functions of Phosphoinositides 392 8.7 Ca2p 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 Ca2p/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