Signal Transduction

3rd Edition - October 23, 2015

Author: ljsbrand M. Kramer

Hardback ISBN:

9 7 8 - 0 - 1 2 - 3 9 4 8 0 3 - 8

eBook ISBN:

9 7 8 - 0 - 1 2 - 3 9 4 8 1 9 - 9

A reference on cellular signaling processes, the third edition of Signal Transduction continues in the tradition of previous editions, in providing a historical overview of how… Read more

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A reference on cellular signaling processes, the third edition of Signal Transduction continues in the tradition of previous editions, in providing a historical overview of how the concept of stimulus-response coupling arose in the early twentieth century and shaped our current understanding of the action of hormones, cytokines, neurotransmitters, growth factors and adhesion molecules. In a new chapter, an introduction to signal transduction, the book provides a concise overview of receptor mechanisms, from receptor – ligand interactions to post-translational modifications operational in the process of bringing about cellular changes. The phosphorylation process, from bacteria to men, is discussed in detail.

Signal transduction third edition further elaborates on diverse signaling cascades within particular contexts such as muscle contraction, innate and adaptive immunity, glucose metabolism, regulation of appetite, oncogenic transformation and cell fate decision during development or in stem cell niches. The subjects have been enriched with descriptions of the relevant anatomical, histological, physiological or pathological condition.

Biography
Preface
Chapter 1. Prologue: Signal Transduction from an Historical Perspective
- Transduction, the word and its meaning
- Irritability, a vital phenomenon
- Protoendocrinologists
- Hormones and neurotransmitters
- The receptive substance
- Proto-messengers and -receptors
- Growth factors: setting the framework
- Problems with nomenclature
Chapter 2. An Introduction to Signal Transduction
- Cells need ways to create symbolic representations of their (changing) environment
- First messengers
- First-messenger signals are ambiguous: their meaning is embedded in context
- The plasma membrane barrier, membrane receptors, and signal transduction
- Receptors and their ligands
- Five types of receptors
- Signaling mechanisms
- Wired allostery and thoughtful decisions
- Posttranslational modifications involved in signaling events
- Focus on nucleotide exchange
- A brief definition of effectors
- Focus on protein phosphorylation
- Protein kinases catalyze the phosphate transfer
- Protein domains, their folds, and their graphic representations
- Which amino acids are susceptible to phosphorylation?
- Bacterial exceptions: phosphoenolpyruvate as phosphate donor and histidine kinases as environmental sensors
- Substrate phosphorylation motifs and distal docking sites
- Protein kinase activation mechanisms
- Protein phosphatases
- PPP1R12A (MYPT1) as an example of how a regulatory subunit controls substrate selectivity (of PP1CC)
- Regulation by intramolecular domain interaction, the example of PTPN6 (SHP-1)
- Decision-making in glycogen synthesis and breakdown: concerted action of kinases and phosphatases
- Signal termination
Chapter 3. Regulation of Muscle Contraction by Adrenoceptors
- Catecholamines
- α- and β-adrenoceptors
- Adrenaline-binding and G-protein-coupling mechanisms
- Adrenoceptor agonists, antagonists, and inverse agonists
- How do ligand-binding characteristics translate into signaling effects?
- Adenylyl cyclase
- cAMP-binding proteins
- Phospholipase C
- Muscle contraction: striated versus smooth muscle
- Contraction waves in the heart
- Adrenaline as a cardiac ino- and chronotrope messenger
- Arresting the β-adrenoreceptor signal: pathway switching and the role of G-protein receptor kinase and arrestin
- α1-adrenoceptors and visceral vasoconstriction
- Adrenaline (again)
Chapter 4. Cholinergic Signaling and Muscle Contraction
- Acetylcholine
- Cholinergic receptor subtypes; nicotinic and muscarinic
- Nicotinic acetylcholine receptors
- Muscarinic acetylcholine receptors
- Type IV nicotinic AChR induces skeletal muscle contraction
- Acetylcholine, acting on the M2-receptor, reduces force and slows down the heart rate
- Phosphodiesterases
- Acetylcholine, acting on the M3 receptor, causes airway constriction and mucus secretion
- Acetylcholine and the induction of nitric oxide, a potent vasodilator
- Neurotransmitters that function with both ionotropic and metabotropic signaling mechanisms
Chapter 5. Sensory Signal Processing; Visual Transduction and Olfaction
- Visual transduction
- Ocular photoreceptor cells
- Photoreceptor mechanisms
- Electric activity of rod cells
- Sensitivity of photoreceptors and adaptation to changing light intensities
- Note on phototransduction in invertebrates
- Olfaction
- Olfactory epithelium
- Odorant receptor signaling
- Other signaling pathways involved in chemosensing
- Pheromone reviews
- The GPCR superfamily
Chapter 6. Intracellular Calcium
- A new second messenger is discovered
- Free, bound, and trapped Ca²⁺
- Cytosolic Ca²⁺ is kept low
- Ca²⁺-binding proteins
- Ca²⁺ receptors
- Ca²⁺/calmodulin-mediated regulation of protein activity
- Tools to study the role of Ca²⁺ in cellular processes
- Mechanisms that elevate cytosol Ca²⁺ concentration
- Decoding Ca²⁺ oscillations
- Mobilizing Ca²⁺ through cyclic ADP ribose, NAADP, and sphingosine-1-phosphate
- Ca²⁺ in action
- Michael Abercrombie a pioneer in cell migration
Chapter 7. Bringing the Signal into the Nucleus: Regulation of Gene Expression
- Gluconeogenesis
- Glucagon and glucocorticoids augment gluconeogenesis
- Signaling through the glucagon receptor
- Protein kinase A
- AKAP, anchoring and scaffolding
- Activation of PKA by cAMP
- PKA substrates involved in gluconeogenesis
- CREB, a nuclear target of PKA
- CREB is member of the basic leucine zipper (bZIP) family of proteins
- Transcription and transcription factors
- Ser133-phosphorylated CREB recruits coactivators CREBBP, PE300, and CRTC2
- CREB stimulates the gluconeogenic program
- Glucagon and cortisol (glucocorticoid) cooperate
- Insulin causes disassembly of the CREB-mediated PIC
- Diabetes and enhanced gluconeogenesis
Chapter 8. Nuclear Receptors
- Steroid hormones
- Steroids accumulate in the nucleus
- Steroids regulate gene transcription
- A superfamily of nuclear receptors
- Domain architecture and general structure of the DNA–protein complex
- Nuclear receptors in context: cross-talk with other transcription factors
- Non-genomic signaling modes of nuclear receptors
- Three precise descriptions of steroids in action in the context of pregnancy
Chapter 9. Protein Kinase C in Oncogenic Transformation and Cell Polarity
- Discovery of a phosphorylating activity independent of cAMP
- The protein kinase C family
- Structural composition of protein kinase C
- Priming and activation of conventional and novel protein kinase C
- Priming and activation of atypical protein kinase C
- Multiple sources of diacylglycerol and other lipids to regulate protein kinase C
- Differential localization of protein kinase C isoforms
- Different types of protein kinase C-binding proteins
- Holding back the PKC response
- Protein kinase C in the context of oncogenic transformation
- Atypical protein kinase C and the regulation of cell polarity
- Atypical protein kinase C in cell migration and axonal outgrowth
Chapter 10. Regulation of Cell Proliferation by Receptor Tyrosine Protein Kinases
- Introduction
- Spotting phosphotyrosine
- v-Src and other protein tyrosine kinases
- Focus on the ERBB receptor family, their ligands, and their dimer partners
- Cross-linking of receptors causes activation
- Oncogenenic mutations
- Protein domains that bind phosphotyrosines and the assembly of signaling complexes
- Branching of the signaling Pathway
- Fine tuning the RAS–MAP-kinase pathway: scaffold proteins
- Termination of the ERK1/2 response
- A family of MAP-kinase-related proteins
- MAP kinases in other organisms
- Other branches of the EGFR signaling pathways
Chapter 11. Signal Transduction to and from Adhesion Molecules
- Adhesion molecules
- Naming names
- Immunoglobulin superfamily
- Claudins
- Occludins
- Integrins
- Cadherins
- Selectins
- Cartilage link proteins
- Integrins, cell survival, and cell proliferation
- Signaling from cadherin clusters
Chapter 12. WNT Signaling and the Regulation of Cell Adhesion and Differentiation
- Destabilization of adherens junctions causes cellular dedifferentiation
- The discovery of the Wnt family of cytokines
- Wnt signals through β-catenin
- Switching TCF from a repressor to an activator
- Adenomatous polyposis coli and the regulation of subcellular localization of β-catenin
- Take your partner: which way β-catenin?
- WTN signaling disables the AXIN–APC destruction complex
- Regulation of gene transcription by β-catenin
- More about the TCF family
- Wnt target genes with a Wnt-enhancer element
- Extracellular inhibitors of Wnt and its receptors
- Contribution of different species to the elucidation of the WNT signal transduction pathway
- Wnt signaling and stem cell self-renewal
- WNT and planar cell polarity
- Mutations of CTNNB1, AXIN, and APC in human cancers
Chapter 13. Activation of the Innate Immune System: The Toll-Like Receptor-4 and Signaling through Ubiquitinylation
- Introduction
- Sensing the microbial universe
- Signaling through the TLR4 receptor
- The IRF family of transcription factors
- Negative feedback control of the TLR4 pathway
- Some consequences of TLR4-induced gene transcription
- Essay: Ubiquitinylation and Sumoylation
Chapter 14. Chemokines and Traffic of White Blood Cells
- Inflammation and leukocytes
- Inflammatory mediators
- Tumor necrosis factor: potential antitumor agent or inflammatory cytokine?
- The family of TNF proteins and receptors
- TNF and regulation of adhesion molecule expression in endothelial cells
- Chemokines and activation of integrins on leukocytes
- Cellular protrusions aid in probing permissive sites on the endothelial surface
- Migration within the tissue
- The three-step process of leukocyte adhesion to endothelial cells
Chapter 15. Activating the Adaptive Immune System: Role of Non-receptor Tyrosine Kinases
- The family of non-receptor protein tyrosine kinases
- T-cell receptor signaling
- Down-regulation of the TCR response
- The lipid raft hypothesis
- Signaling through the interferon receptors
- Oncogenes, malignancy, and signal transduction
- Essay: non-receptor PTKs and their regulation
Chapter 16. Signaling through the Insulin Receptor: Phosphoinositide 3-Kinases and AKT
- Insulin receptor-signaling: it took a little time to work out the details
- Signaling through phosphoinositides
- Phosphatidyl inositol 3-kinase
- Studying the role of PI3-kinase with inhibitors
- Pathways of activation for PI3-kinase
- AKT and activation through PI-3,4,5-P3
- Insulin: the role of IRS, PI3-kinase and AKT in the regulation of glycogen synthesis
- The role of PI3-kinase in activation of protein synthesis
- RHEB and TSC
- Integration of growth factor and nutrient signaling
- PI3-kinase, regulator of cell size, proliferation, and transformation
- Other processes mediated by the 3-phosphorylated inositol phospholipids
Chapter 17. TGFβ and Signaling through Receptor Serine/Threonine Protein Kinases
- The TGFβ family of growth factors
- TGFβ receptors, type-I and type-II
- TGFβ-mediated receptor activation
- Accessory and pseudo-receptors: TGFBR3, ENG, TDGF1, and BAMBI
- Downstream signaling: Drosophila, Caenorhabditis, and Smad
- SMAD proteins have multiple roles in signal transduction
- Regulation of Transcription by SMAD Proteins
- Cooperation with other pathways and other transcription factors
- Holding the TGFβ pathway in check
- TGFβ: tumor suppressor and metastatic promoter?
- Noncanonical pathways
Chapter 18. Protein Phosphatases
- Introduction
- Protein tyrosine phosphatases
- Protein serine/threonine phosphatases
Chapter 19. Cell Fate Determination by Notch
- Notched wings, Morgan, and the gene theory
- One gene, many alleles
- Membrane components of the Notch pathway
- Activation of NOTCH1
- Destruction of the NOTCH1-intracellular domain, Nicd
- Both receptor and ligand trafficking are essential for NOTCH signaling
- NOTCH in drosophila development
- Notch in the maintenance of an intestinal stem compartment
- Cross-talk with other signal transduction pathways
- Notch and disease
Index

ljsbrand M. Kramer

Ijsbrand Kramer is a professor at the University of Bordeaux, working in the European Institute of Chemistry and Biology (IECB). He holds a Bachelors and Masters degree in BioMedicine from the University of Utrecht, The Netherlands, with a one year research-excursion in the Department of Cell Biology at the University of Liverpool, UK. He did his Ph.D. at the University of Amsterdam, in the Central Laboratory of Blood transfusion services (Stichting Sanquin) and worked as a post-doctoral fellow at the Hubrecht Laboratory in Utrecht and at the University of Washington in Seattle. He then took a lecturer position at the Department of Pharmacology at University College London, where he taught Signal Transduction (with Bastien Gomperts and Pether Tatham) and Pharmacology. Both teaching activities have been documented in textbooks: Signal Transduction (3 editions) and Receptor Pharmacology (CRC Press/Taylor Francis Group, 3 editions). Most of his research centers on the theme of inflammation, starting with neutrophils and the NADPH oxidase, synovial fibroblasts and destruction of the joint and more recently podosomes formation and extracellular matrix destruction in vascular endothelium. He moved to the University of Bordeaux for family reasons and switched from Pharmacology to Cell Biology, with a strong contribution to an introductory course for 1st year university students. Given the important teaching load and the general low level of student engagement in higher education he started to investigate the reasons for student failure (finding out about their expectations and attitudes) and the role of images and animations in comprehension. Scientific publications, web-based multimedia resources and dramatically enhanced retention rates (from 33 to 85%) are the fruits of these activities. At the same time he organized with University College London and Universitat Pompeu Fabra, Barcelona, summer schools on Receptor and Signalling Mechanism. He has been co-director of two European Programmes (Interbio and Transbio) that aimed at enhancing industrial innovation in the biomedical sector in the South West European Region (SUDOE).

For book/publicity purposes, image of the author by Maarten Kramer

Affiliations and expertise

University of Bordeaux, Talence, France