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Structure and function in cell signalling / John Nelson. — Chichester, England ;Hoboken, NJ : John Wiley & Sons, c2008. – (58.1483/N425) |
Contents
Contents
AcknowLedgments
Preface
1 The components and foundations of signaling
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 in amoebazoans 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
References
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 PH domains
3.5 Bcl-2 homotogy (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
References
4 Protein kinase enzymes - activation and auto-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 Cyctin dependent kinases
4.5 Secondary inhibition mechanisms- PKA
References
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 Anchoring Proteins
5.8 Phosphorylase kinase
5.9 Glycogen phosphorylase
5.10 Glycogen synthase
5.11 Remaining questions - scaffolds and alternate second messenger 'receptors'
5.12 G protein coupled receptor kinases - downregutators， signal integrators
References
6 Single pass growth factor receptors
6.1 Receptor tyrosine kinases - ligands and signal transduction
6.2 The PDGFR family - signal transduction
6.3 PDGFR family autoinhibition: juxtamembrane and A-loop tyrosines
6.4 Crystal structure of kinase domain of PDGFR famiLy-A member: Fit-3
6.5 The ErbB family
6.6 ErbB-type receptor signal transduction particles
6.7 Autoinhibition of EGFR and activation
References 211
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 sefine/threonine kinase family of Ras effectors
7.4 Ras protein structure and function
7.5 The switch mechanism: hydroLysis-driven conformational change in Ras
7.6 GTP hydrolysis
7.7 Effector and regulator binding surfaces of Ras
References
8 G proteins (II) - heterotrimeric G proteins
8.1 Classification and structural relationship with Ras
8.2 Gα-subunits: the Ras-like core， G-boxes and switch regions
8.3 GTP exchange， hydrolysis and switch movements
8.4 β/γ- and receptor-binding surfaces of α-subunits
8.5 Modulators of G protein activity - the 'RGS' protein family
8.6 Signal transduction byβ/γ subunits
References
9 The insulLin receptor and the anabolic response
9.1 The insulin receptor - a pre-dimerised RTK with a unique substrate
9.2 InsR and IGF-IR: differentiation leads differential tissue effects
9.3 Features of metabolic control in key tissues
9.4 InsR downstream signalling pathways
9.5 The insulin receptor substrate - a surrogate signal transduction particle
9.6 IRS-1/2 phosphoryiation and PI-3-kinase activation
9.7 Protein phosphatase-1 (PP-1)
9.8 InsuLin reverses effects of adrenaline and/or gtucagon
9.9 PTP3 downstream effects - glycogen synthesis
9.10 Many questions remain
References
10 Mitogens and cell cycle progression
10.1 The mitogenic response and the ceLL division cycle
10.2 GO， competency， and the point of no return in G1 - the 'R-point'
10.3 Oncogene products derived from growth factor pathway components
10.4 Transcription and cyclins
10.5 Cyclin dependent kinases
10.6 Deactivation by cydin destruction
10.7 Cyclin dependent kinases - activation through cyclin synthesis
10.8 Mitogenic pathway downstream of single pass tyrosine kinase receptors
10.9 CydinD/Cdk-4/6 - only important substrate is RB
10.10 Retinoblastoma-related 'pocket proteins' - negative modulators of E2F
10.11 De-repression of the cyctin E gene by cycUn D/Cdk-4/6
10.12 Cyctin A/Cdk-2 - S-phase progression and termination
10.13 The controtlled process of mammatian DNA replication
10.14 Cyctin B translocations and N-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
References
Appendix 1: Worked examples
A.1 Enzyme and receptor assays worked out from raw data examples
Appendix 2: RasMoh instattation and use
Index
