Structure and Function in Cell Signalling

by Nelson, John

• ISBN13: 9780470025505
• ISBN10: 0470025506
• Edition: 1st
• Format: Hardcover
• Copyright: 2008-08-04
• Publisher: WILEY

Summary

"This book contains extremely detailed and informative content on structure and function of ligands, receptors, and signalling intermediates plus interactions ... the extent of detail and appropriate referencing is impressive." -Microbiology Today, July 2009"A very well-written book suitable for use as a reference or textbook for an undergraduate subject in cell signalling. For researchers interested in the molecular basis of cell signalling and how aberrant regulation of cell signalling proteins causes diseases, this is an excellent resource of biochemical and structural information." -Australian Biochemist, August 2009"From basics to details, this is an elegantly written and carefully edited book. The chapters on cell cycle control and oncogenesis are particularly fascinating and valuable to biomedical research. This is the book to have if you are interested in molecular mechanisms of signal transduction. It is a great introduction to the literature that will be welcomed by students and experts alike." -Doody's, January 2009This text is a concise and accessible introduction to the dynamic but complex field of signal transduction. Rather than simply cataloguing all signalling molecules and delineating every known pathway, this book aims to break signalling down into common elements and activities - the 'nuts and bolts' of cellular information exchange.With an emphasis on clarity of presentation throughout, the book teaches the basic principles focusing on a mature core of knowledge, providing students with a foundation of learning in this complex and potentially confusing subject. It also addresses the issue of variation in the numbering of key amino acids as well as featuring interaction with RasMol software, and exercises to aid understanding. An accessible introduction to the complex field of cell signalling Interacts with RasMol software - freely downloadable for viewing structures in 3D Includes exercises and clear instructions in the use of RasMol Well illustrated in full colour throughoutStructure and Function in Cell Signalling is an invaluable resource to students across a range of life science degree programmes including biochemistry, cell and molecular biology, physiology, biomedicine and oncology. This book provides a clear, accessible introduction to this rapidly expanding field.

Author Biography

John Nelson, Queen's University, Belfast, UK.

Table of Contents

Acknowledgments

Preface

The components and foundations of signalling

Definition of terms used

Historical foundations

Early milestones in signal transduction research

The discovery of receptors and G proteins

cAMP pathways

cAMP: ancient hunger signal - primitive signalling in amoebazoans and prokaryotes

References

Enzymes and receptors - quantitative aspects

Enzyme steady state assays - Michaelian enzymes

Receptor equilibrium binding assays

The receptor's environment

Guanine nucleotides and the agonist 'affinity-shift' of 7-pass receptors

References

Modules and motifs in transduction

Src homology domains

PH superfold modules: PH-, PTB- and PDZ-domains

Bcr-homology (BcrH) domains

Dbl homology (DH) domains - partners of PH domains

Bcl-2 homology (BH) domains

Ras binding domains

Phosphoserine/phosphothreonine-binding domains

EF-hands - calcium-sensing modules

C1 and C2 domains - a Ca2þ-activated, lipid-binding, module

References

Protein kinase enzymes - activation and auto-inhibition

The protein kinase fold

Protein kinases activated by A-loop phosphorylation

The insulin receptor kinase (IRK) - a 'gated' kinase

Cyclin dependent kinases

Secondary inhibition mechanisms - PKA

References

7-pass receptors and the catabolic response

7-pass receptor phylogeny

Functional mechanisms of 7-pass receptors

Amplification

Adenylyl cyclase - signal limitation

Adenylyl cyclase isoforms

G proteins and the adenylyl cyclase effector isoforms

Regulatory subunits of PKA and A-Kinase Anchoring Proteins

Phosphorylase kinase

Glycogen phosphorylase

Glycogen synthase

Remaining questions - scaffolds and alternate second messenger 'receptors'

G protein coupled receptor kinases - downregulators, signal integrators

References

Single pass growth factor receptors

Receptor tyrosine kinases - ligands and signal transduction

The PDGFR family - signal transduction

PDGFR family autoinhibition: juxtamembrane and A-loop tyrosines

Crystal structure of kinase domain of PDGFR family-A member: Flt-3

The ErbB family

ErbB-type receptor signal transduction particles

Autoinhibition of EGFR and activation

References

G proteins (I) - monomeric G proteins

Classification

ON and OFF states of Ras-like proteins

Raf - a multi-domain serine/threonine kinase family of Ras effectors

Ras protein structure and function

The switch mechanism: hydrolysis-driven conformational change in Ras

GTP hydrolysis

References

G proteins (II) - heterotrimeric G proteins

Classification and structural relationship with Ras

Ga-subunits: the Ras-like core, G-boxes and switch regions

GTP exchange, hydrolysis and switch movements

b/g- and receptor-binding surfaces of a-subunits

Modulators of G protein activity - the 'RGS' protein family

Signal transduction by b/c subunits

References

The insulin receptor and the anabolic response

The insulin receptor - a pre-dimerised RTK with a unique substrate

InsR and IGF-IR: differentiation leads differential tissue effects

Features of metabolic control in key tissues

InsR downstream signalling pathways

The insulin receptor substrate -

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