Structure and Function in Cell Signalling / Edition 1

Structure and Function in Cell Signalling / Edition 1

by John Nelson
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Structure and Function in Cell Signalling / Edition 1

"This book contains extremely detailed and informative contenton structure and function of ligands, receptors, and signallingintermediates plus interactions … the extent of detail andappropriate referencing is impressive." –MicrobiologyToday, July 2009

"A very well-written book suitable for use as a reference ortextbook for an undergraduate subject in cell signalling. Forresearchers interested in the molecular basis of cell signallingand how aberrant regulation of cell signalling proteins causesdiseases, this is an excellent resource of biochemical andstructural information." –Australian Biochemist, August2009

"From basics to details, this is an elegantly written andcarefully edited book. The chapters on cell cycle control andoncogenesis are particularly fascinating and valuable to biomedicalresearch. This is the book to have if you are interested inmolecular mechanisms of signal transduction. It is a greatintroduction to the literature that will be welcomed by studentsand experts alike." –Doody's, January 2009

This text is a concise and accessible introduction to thedynamic but complex field of signal transduction. Rather thansimply cataloguing all signalling molecules and delineating everyknown pathway, this book aims to break signalling down into commonelements and activities – the ‘nuts and bolts’ ofcellular information exchange.

With an emphasis on clarity of presentation throughout, the bookteaches the basic principles focusing on a mature core ofknowledge, providing students with a foundation of learning in thiscomplex and potentially confusing subject. It also addresses theissue of variation in the numbering of key amino acids as well asfeaturing interaction with RasMol software, and exercises to aidunderstanding.

  • An accessible introduction to the complex field of cellsignalling
  • Interacts with RasMol software – freely downloadable forviewing structures in 3D
  • Includes exercises and clear instructions in the use ofRasMol
  • Well illustrated in full colour throughout

Structure and Function in Cell Signalling is aninvaluable resource to students across a range of life sciencedegree programmes including biochemistry, cell and molecularbiology, physiology, biomedicine and oncology. This book provides aclear, accessible introduction to this rapidly expanding field.

Product Details

ISBN-13: 9780470025512
Publisher: Wiley
Publication date: 09/02/2008
Pages: 410
Product dimensions: 6.60(w) x 9.50(h) x 0.90(d)

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Table of Contents



1 The components and foundations of signalling.

1.1 Definition of terms used.

1.2 Historical foundations.

1.3 Early milestones in signal transduction research.

1.4 The discovery of receptors and G proteins.

1.5 cAMP pathways.

1.6 cAMP: ancient hunger signal – primitive signalling inamoebazoans and prokaryotes.


2 Enzymes and receptors – quantitative aspects.

2.1 Enzyme steady state assays – Michaelian enzymes.

2.2 Receptor equilibrium binding assays.

2.3 The receptor’s environment.

2.4 Guanine nucleotides and the agonist‘affinity-shift’ of 7-pass receptors.


3 Modules and motifs in transduction.

3.1 Src homology domains.

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

3.3 Bcr-homology (BcrH) domains.

3.4 Dbl homology (DH) domains – partners of PHdomains.

3.5 Bcl-2 homology (BH) domains.

3.6 Ras binding domains.

3.7 Phosphoserine/phosphothreonine-binding domains.

3.8 EF-hands – calcium-sensing modules.

3.9 C1 and C2 domains – a Ca2+-activated,lipid-binding, module.


4 Protein kinase enzymes – activation andauto-inhibition.

4.1 The protein kinase fold.

4.2 Protein kinases activated by A-loop phosphorylation.

4.3 The insulin receptor kinase (IRK) – a‘gated’ kinase.

4.4 Cyclin dependent kinases.

4.5 Secondary inhibition mechanisms – PKA.


5 7-pass receptors and the catabolic response.

5.1 7-pass receptor phylogeny.

5.2 Functional mechanisms of 7-pass receptors.

5.3 Amplification.

5.4 Adenylyl cyclase – signal limitation.

5.5 Adenylyl cyclase isoforms.

5.6 G proteins and the adenylyl cyclase effector isoforms.

5.7 Regulatory subunits of PKA and A-Kinase AnchoringProteins.

5.8 Phosphorylase kinase.

5.9 Glycogen phosphorylase.

5.10 Glycogen synthase.

5.11 Remaining questions – scaffolds and alternate secondmessenger ‘receptors’.

5.12 G protein coupled receptor kinases – downregulators,signal integrators.


6 Single pass growth factor receptors.

6.1 Receptor tyrosine kinases – ligands and signaltransduction.

6.2 The PDGFR family – signal transduction.

6.3 PDGFR family autoinhibition: juxtamembrane and A-looptyrosines.

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

6.5 The ErbB family.

6.6 ErbB-type receptor signal transduction particles.

6.7 Autoinhibition of EGFR and activation.


7 G proteins (I) – monomeric G proteins.

7.1 Classification.

7.2 ON and OFF states of Ras-like proteins.

7.3 Raf – a multi-domain serine/threonine kinase family ofRas effectors.

7.4 Ras protein structure and function.

7.5 The switch mechanism: hydrolysis-driven conformationalchange in Ras.

7.6 GTP hydrolysis.


8 G proteins (II) – heterotrimeric G proteins.

8.1 Classification and structural relationship with Ras.

8.2 Ga-subunits: the Ras-like core, G-boxes and switchregions.

8.3 GTP exchange, hydrolysis and switch movements.

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

8.5 Modulators of G protein activity – the‘RGS’ protein family.

8.6 Signal transduction by b/c subunits.


9 The insulin receptor and the anabolic response.

9.1 The insulin receptor – a pre-dimerised RTK with aunique substrate.

9.2 InsR and IGF-IR: differentiation leads differential tissueeffects.

9.3 Features of metabolic control in key tissues.

9.4 InsR downstream signalling pathways.

9.5 The insulin receptor substrate – a surrogate signaltransduction particle.

9.6 IRS-1/2 phosphorylation and PI-3-kinase activation.

9.7 Protein phosphatase-1 (PP-1).

9.8 Insulin reverses effects of adrenaline and/or glucagon.

9.9 PIP3 downstream effects – glycogen synthesis.

9.10 Many questions remain.


10 Mitogens and cell cycle progression.

10.1 The mitogenic response and the cell division cycle.

10.2 G0, competency, and the point of no return in G1 –the ‘R-point’.

10.3 Oncogene products derived from growth factor pathwaycomponents.

10.4 Transcription and cyclins.

10.5 Cyclin dependent kinases.

10.6 Deactivation by cyclin destruction.

10.7 Cyclin dependent kinases – activation through cyclinsynthesis.

10.8 Mitogenic pathway downstream of single pass tyrosine kinasereceptors.

10.9 CyclinD/Cdk-4/6 – only important substrate is RB.

10.10 Retinoblastoma-related ‘pocket proteins’– negative modulators of E2F.

10.11 De-repression of the cyclin E gene by cyclinD/Cdk-4/6.

10.12 Cyclin A/Cdk-2 – S-phase progression andtermination.

10.13 The controlled process of mammalian DNA replication.

10.14 Cyclin B translocations and M-phase.

10.15 Cdk inhibitors.

10.16 p53 cell cycle arrest and apoptosis.

10.17 7-pass receptors and mitosis.

10.18 Concluding remarks and caveats.


Appendix 1: Worked examples.

A.1 Enzyme and receptor assays worked out from raw dataexamples.

A.1.1 An alkaline phosphatase assay.

Appendix 2: RasMol: installation and use.


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