Signal transduction / IJsbrand M. Kramer -- 3rd ed. -- Amsterdam : Academic Press is an imprint of Elsevier, 2016. – (58.1574 /G634/3rd ed.)

Contents

Biography

Preface

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

References

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

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 I'q'PN6 (SHP-1)

Decision-making in glycogen synthesis and breakdown: concerted action of kinases and phosphatases

Signal termination

References

3. Regulation of Muscle Contraction by Adrenoceptors

Catecholamines

α- and [3-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

αl-adrenoceptors and visceral vasoconstriction

Adrenaline (again)

References

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

References

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

Chemosensors

Olfactory epithelium

Odorant receptor signaling

Other signaling pathways involved in chemosensing

Pheromone reviews

The GPCR superfamily

References

6. Intracellular Calcium

A new second messenger is discovered

Free, bound, and trapped Ca2+

Cytosolic Ca2+ is kept low

Ca>-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 Ca> through cyclic ADP ribose, NAADP, and sphingosine-l-phosphate

Ca2+ in action

Michael Abercrombie a pioneer in cell migration

References

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

References

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

Endocrine disruption in a plastic world: the example of bisphenol A

References

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

References

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

The RAS-MAP kinase pathway

Fine tuning the RAS-MAP-kinase pathway: scaffold proteins

Why are the signaling pathways so complicated?

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

References

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

References

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 13-catenin?

WTN signaling disables the AXIN-APC destruction complex

Regulation of gene transcription by [3-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

References

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

References

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

References

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

References

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

Phosphatidy1 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

References

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

References

18. Protein Phosphatases

Introduction

Protein tyrosine phosphatases

Protein serine/threonine phosphatases

References

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 m the maintenance of an intestinal stem compartment

Cross-talk with other signal transduction pathways

Notch and disease

References

Index