Dennis / Bradshaw Transduction Mechanisms in Cellular Signaling

Cell Signaling Collection
1. Auflage 2011
ISBN: 978-0-12-383863-6
Verlag: Elsevier Science & Techn.
Format: PDF
Kopierschutz: 1 - PDF Watermark

E-Book, Englisch, 610 Seiten, Web PDF

Cytosol, the liquid found inside cells, is the site for multiple cell processes, including signaling from the cell membrane to sites within the cell. Cytosolic signaling mechanisms are researched and studied in graduate programs in cell biology, molecular biology, biochemistry, pharmacology, molecular and cellular physiology, pharmacy, and biomedical sciences. - Articles written and edited by experts in the field - Thematic volume covering material needed for young professionals joining the field of research and graduate students taking survey courses - Up-to-date research on signaling systems and mutations in transcription factors that provide new targets for treating disease

Autoren/Hrsg.

Dennis, Edward A.

Bradshaw, Ralph A.

Inhaltsverzeichnis

1;Front Cover;1
2;Transduction Mechanisms in Cellular Signaling;4
3;Copyright Page;5
4;Editorial Advisory Board;6
5;Contents;8
6;Preface;12
7;Contributors;14
8;Section A: Overview;18
8.1;Chapter 1: Intracellular Signaling ;20
8.1.1;Origins of Cell Signaling Research;20
8.1.2;Intracellular Signaling Mechanisms;21
8.1.3;Focus and Scope of this Volume;23
8.1.4;References;24
9;Section B: Phosphorylation/Dephosphorylation;26
9.1;Part 1: Kinases;28
9.1.1;Chapter 2: Eukaryotic Kinomes: Genomics and Evolution of Protein Kinases;30
9.1.1.1;Introduction;30
9.1.1.2;The Human Kinome;30
9.1.1.3;Comparative Kinomics;32
9.1.1.4;Saccharomyces cerevisiae;32
9.1.1.5;Caenorhabditis elegans;33
9.1.1.6;Drosophila melanogaster;33
9.1.1.7;Emergence and Diversity of Vertebrate Kinomes;33
9.1.1.8;Coda;33
9.1.1.9;References;34
9.1.2;Chapter 3: Modular Protein Interaction Domains in Cellular Communication;36
9.1.2.1;Introduction;36
9.1.2.2;Phosphotyrosine-Dependent Protein – Protein Interactions;36
9.1.2.3;Interaction Domains: a Common Theme in Signaling;40
9.1.2.4;Interaction Domains in the Evolution of Signaling Pathways;43
9.1.2.5;Emergent Properties of Modular Protein Interaction Domain-Driven Signaling Networks;44
9.1.2.6;Acknowledgements;45
9.1.2.7;References;45
9.1.3;Chapter 4: Recognition of Phospho-Serine/Threonine Phosphorylated Proteins by Phospho-Serine/Threonine-Binding Domains ;50
9.1.3.1;Introduction;50
9.1.3.2;14-3-3 Proteins;50
9.1.3.3;FHA Domains;51
9.1.3.4;WW Domains;53
9.1.3.5;Polo-Box Domains;54
9.1.3.6;Tandem Brct-Repeat Domains;55
9.1.3.7;Tandem Brct-Repeat Domains;56
9.1.3.8;Concluding Remarks;56
9.1.3.9;Acknowledgements;57
9.1.3.10;References;57
9.1.4;Chapter 5:Protein Kinase Inhibitors;62
9.1.4.1;Signal Transduction Therapy and Protein Kinase Inhibitors;62
9.1.4.2;Protein Tyrosine Kinase Inhibitors;62
9.1.4.3;Ser/Thr Kinase Inhibitors;66
9.1.4.4;References;69
9.1.5;Chapter 6: Principles of Kinase Regulation;72
9.1.5.1;Introduction;72
9.1.5.2;Protein Kinase Structure;72
9.1.5.3;General Principles of Control;72
9.1.5.4;Regulatory Sites in Protein Kinase Domains;74
9.1.5.5;Conclusions;75
9.1.5.6;References;75
9.1.6;Chapter 7: Mammalian MAP Kinases;78
9.1.6.1;Introduction;78
9.1.6.2;The ERK Group of MAP Kinases;78
9.1.6.3;The P38 Group of MAP Kinases;81
9.1.6.4;The JNK Group of MAP Kinases;82
9.1.6.5;MAP Kinase Docking Interactions;82
9.1.6.6;Scaffold Proteins;83
9.1.6.7;KSR;83
9.1.6.8;MP-1;84
9.1.6.9;MORG1;84
9.1.6.10;JIP;84
9.1.6.11;POSH;85
9.1.6.12;OSM;86
9.1.6.13;References;86
9.1.7;Chapter 8: The Negative Regulation ofJAK/STAT Signaling;92
9.1.7.1;Introduction;92
9.1.7.2;Modulation of JAK Kinase Activity by Extrinsic Kinases;95
9.1.7.3;Protein Inhibitors of Activated Stats (PIAS);95
9.1.7.4;Suppressors of Cytokine Signaling;97
9.1.7.5;Future Outlook;99
9.1.7.6;Acknowledgements;100
9.1.7.7;References;100
9.1.8;Chapter 9: Protein Proximity Interactions;106
9.1.8.1;Advances in the Analysis of Protein – Protein Interactions;106
9.1.8.2;Subcellular Structures and Multiprotein Complexes that Contribute to Cell Signaling;106
9.1.8.3;Kinase and Phosphatase Targeting;106
9.1.9;Chapter 10: Global Analysis of PhosphoregulatoryNetworks;108
9.1.9.1;Introduction;108
9.1.9.2;Global Mapping of Phosphorylation;108
9.1.9.3;Global Mapping of Phosphorylationglobal Identification of Kinase – Substrate Pairs;113
9.1.9.4;Conclusion;116
9.1.9.5;References;116
9.2;Part 2: Phosphatases;120
9.2.1;Chapter 11: Phosphatase Families DephosphorylatingSerine and Threonine Residues in Proteins;122
9.2.1.1;Current Classification of Protein Serine/Threonine Phosphatases;122
9.2.1.2;Background;122
9.2.1.3;Evolution and Conserved Features of the PPP Family;124
9.2.1.4;Holoenzyme Structures of PPP Family Members;126
9.2.1.5;Catalytic Activities of the PPP Family Members;129
9.2.1.6;Functions of PPP Family Members;130
9.2.1.7;Medical Importance of the PPP Family;131
9.2.1.8;The PPM Family;132
9.2.1.9;The FCP Family;132
9.2.1.10;Concluding Remarks;132
9.2.1.11;Acknowledgements;137
9.2.1.12;References;137
9.2.2;Chapter 12: The Structure and Topology of ProteinSerine/Threonine Phosphatases;140
9.2.2.1;Introduction;140
9.2.2.2;Protein Serine/Threonine Phosphatases of the PPP Family;140
9.2.2.3;Protein Serine/Threonine Phosphatases of the PPM Family;143
9.2.2.4;Conclusions;143
9.2.2.5;References;144
9.2.3;Chapter 13: SH2 Domain-Containing Protein-TyrosinePhosphatases;146
9.2.3.1;History and Nomenclature;146
9.2.3.2;Structure, Expression, and Regulation;146
9.2.3.3;Biological Functions of Shps;151
9.2.3.4;Shp Signaling and Substrates;154
9.2.3.5;Determinants of Shp Specificity;167
9.2.3.6;Shps and Human Disease;167
9.2.3.7;Summary and Future Directions;169
9.2.3.8;Acknowledgements;170
9.2.3.9;References;170
9.2.4;Chapter 14: Calcineurin;186
9.2.4.1;Introduction;186
9.2.4.2;Enzymatic Properties;186
9.2.4.3;Structure;187
9.2.4.4;Regulation;187
9.2.4.5;Distribution and Isoforms;188
9.2.4.6;Functions;188
9.2.4.7;Conclusion;190
9.2.4.8;References;190
9.2.5;Chapter 15: Protein Serine/Threonine-Phosphatase2C (PP2C);192
9.2.5.1;Introduction;192
9.2.5.2;PP2C Functions Conserved in Both Lower and Higher Eukaryotes;192
9.2.5.3;PP2C Functions Specific in Higher Eukaryotes;193
9.2.5.4;References;195
9.2.6;Chapter 16 Inhibitors of Protein TyrosinePhosphatases;198
9.2.6.1;Introduction;198
9.2.6.2;Covalent PTP Modifiers;198
9.2.6.3;Oxyanions as PTP Inhibitors;200
9.2.6.4;Non-Hydrolyzable pTyr Surrogates as PTP Inhibitors;200
9.2.6.5;Bidentate PTP Inhibitors;202
9.2.6.6;Other PTP Inhibitors;203
9.2.6.7;Concluding Remarks;203
9.2.6.8;Acknowledgement;204
9.2.6.9;References;204
9.2.7;Chapter 17: MAP Kinase Phosphatases;208
9.2.7.1;Introduction;208
9.2.7.2;Ser/Thr Protein Phosphatases and the Regulation of MAPK Activity;208
9.2.7.3;MAPK Regulation by Classical Protein Tyrosine Phosphatases (PTPS);210
9.2.7.4;Mapk Regulation by Dual-Specificity Protein Phosphatases;212
9.2.7.5;Mammalian Dual-Specificity MAPK Phosphatases;213
9.2.7.6;Summary;217
9.2.7.7;Acknowledgements;218
9.2.7.8;References;218
9.2.8;Chapter 18: Protein Phosphatase 2A;224
9.2.8.1;Introduction;224
9.2.8.2;PP2A Regulatory Subunits Mediate Proximity Interactions;224
9.2.8.3;PP2A-Interacting Proteins;233
9.2.8.4;References;233
10;Section C: Lipid Signaling;238
10.1;Chapter 19: Lipid-Mediated Localization ofSignaling proteins;240
10.1.1;Introduction;240
10.1.2;Lipid Modifications on the Cytoplasmic Face of Membranes;240
10.1.3;Lipid Modifications in the Lumen of the Secretory Pathway;242
10.1.4;Localization of Lipid-Modified Proteins;243
10.1.5;Summary;245
10.1.6;Acknowledgements;245
10.1.7;References;245
10.2;Structural Principles of Lipid Second Messenger Recognition;248
10.2.1;Introduction;248
10.2.2;Phospholipid Second Messenger Recognition by Active Sites of Enzymes;248
10.2.3;Phosphoinositide-Binding Domains;252
10.2.4;Non-Phosphoinositide Lipid Messenger Recognition;254
10.2.5;Future Directions;254
10.2.6;Acknowledgements;254
10.2.7;References;254
10.3;Chapter 21: Pleckstrin Homology (PH) Domains;256
10.3.1;Identification and Definition of PH Domains;256
10.3.2;The Structure of PH Domains;256
10.3.3;PH Domains as Phosphoinositidebinding Modules;256
10.3.4;Highly Specific Recognition of Phosphoinositides (and Inositol Phosphates) by PH Domains;257
10.3.5;Binding of PH Domains to Nonphosphoinositide Ligands;260
10.3.6;Possible Roles of Nonphosphoinositide PH Ligands;260
10.3.7;Conclusions;261
10.3.8;References;261
10.4;Chapter 22: PX Domains;266
10.4.1;History and Overview of PX Domains;266
10.4.2;Lipid-Binding Specificity and Structure of PX Domains;266
10.4.3;Physiological Function of PX Domains;269
10.4.4;References;270
10.5;Chapter 23: FYVE Domains in Membrane Traffickingand Cell Signaling;274
10.5.1;Introduction;274
10.5.2;Role For PI(3)P in Membrane Trafficking and Identification of the FYVE Domain;274
10.5.3;Structural Basis for PI(3)P Recognition by the FYVE Domain;275
10.5.4;Conservation of the FYVE Domain and Localization of PI(3)P;276
10.5.5;FYVE Domain-Containing Proteins in Membrane Trafficking;276
10.5.6;FYVE Domain-Containing Proteins Involved in PI(3)P Metabolism;279
10.5.7;FYVE Domain-Containing Proteins in Signaling;280
10.5.8;FYVE-Like Domains;281
10.5.9;Conclusions;281
10.5.10;Acknowledgements;281
10.5.11;References;281
10.6;Chapter 24: Type I Phosphatidylinositol 4-Phosphate5-Kinases (PI4P 5-kinases);286
10.6.1;Introduction;286
10.6.2;Basic Properties;286
10.6.3;Regulation;288
10.6.4;Function;289
10.6.5;Acknowledgements;289
10.6.6;References;289
10.7;Chapter 25: Phosphoinositide 3-Kinases;292
10.7.1;Introduction;292
10.7.2;The Enzymes;292
10.7.3;The Products;293
10.7.4;Phosphatases;294
10.7.5;Lipid Binding Domains;294
10.7.6;Effectors and Responses;296
10.7.7;Genetics;297
10.7.8;Pharmacology;299
10.7.9;Synopsis;299
10.7.10;References;300
10.8;Chapter 26: Inositol Pentakisphosphate: A SignalTransduction Hub;304
10.8.1;Introduction;304
10.8.2;Synthesis of Ins(1,3,4,5,6)P5;304
10.8.3;Functions of Ins(1,3,4,5,6)P 5 as a Precursor Pool;305
10.8.4;Dephosphorylation of Ins(1,3,4,5,6)P 5 To Ins(3,4,5,6)P4;305
10.8.5;Phosphorylation of Ins(1,3,4,5,6)P5 To PP-Insp4;306
10.8.6;Phosphorylation of Ins(1,3,4,5,6)P5 to Insp6;306
10.8.7;Other Functions for Ins(1,3,4,5,6)P 5 : Regulation of Pten;307
10.8.8;An Expanding List of Further Proposed Functions for Ins(1,3,4,5,6)P5;307
10.8.9;Concluding Statement;307
10.8.10;References;308
10.9;Chapter 27: IP3 Receptors;312
10.9.1;Introduction;312
10.9.2;Diversity of IP 3 RS;312
10.9.3;Structure of IP 3 R;313
10.9.4;Regulation of IP 3 Rs by IP3 and Ca2+;314
10.9.5;Modulation of IP 3R;314
10.9.6;Protein Interactions with IP3 R;314
10.9.7;References;315
10.10;Chapter 28: PTEN;318
10.10.1;Introduction;318
10.10.2;PTEN Discovery and Function;318
10.10.3;PTEN and Cancer;318
10.10.4;Mouse Models for PTEN Function;320
10.10.5;PTEN Structure;320
10.10.6;The PTEN Signaling Pathway;320
10.10.7;Haploinsufficiency and Senescence in Cancer;321
10.10.8;PTEN in Cancer Therapy;322
10.10.9;References;322
10.11;Chapter 29: PTEN/MTM PhosphatidylinositolPhosphatases;324
10.11.1;PTEN;324
10.11.2;Myotubularin: A Novel Family of Phosphatidylinositol Phosphatases;326
10.11.3;References;327
10.12;Chapter 30: Diacylglycerol Kinases;328
10.12.1;Abbreviations;328
10.12.2;Introduction;328
10.12.3;The DGK Family;328
10.12.4;Regulation of DGKS;329
10.12.5;Paradigms of DGK Function;330
10.12.6;Conclusions;331
10.12.7;References;331
10.13;Chapter 31: Phospholipase C;334
10.13.1;Introduction;334
10.13.2;PLC Anatomy ;334
10.13.3;PLC Activation Mechanisms;334
10.13.4;PLC- ß;334
10.13.5;PLC- .;335
10.13.6;PLC- d;336
10.13.7;PLC- e;336
10.13.8;PLC Physiology;336
10.13.9;References;337
10.14;Chapter 32: Phospholipase D;340
10.14.1;Introduction;340
10.14.2;THe PLD Gene Family;341
10.14.3;Vesicle Trafficking;343
10.14.4;Endocytosis;343
10.14.5;Exocytosis;343
10.14.6;Signal Transduction;344
10.14.7;PLD, A Potential Drug Target;345
10.14.8;Acknowledgements;346
10.14.9;References;346
10.15;Chapter 33: Role of Phospholipase A2 Forms inArachidonic Acid Mobilization and Eicosanoid Generation;350
10.15.1;Introduction;350
10.15.2;PLA2 Groups;350
10.15.3;Cellular Function in AA Release;351
10.15.4;Cross-Talk Between Cpla2aa and Spla2;352
10.15.5;References;353
10.16;Chapter 34: Prostaglandin Mediators;356
10.16.1;Introduction;356
10.16.2;The Cyclooxygenase Pathway;356
10.16.3;Prostanoid Receptors;357
10.16.4;Thromboxane A2 (TXA2);357
10.16.5;Prostacyclin (PGI2);358
10.16.6;Prostaglandin D2 (PGD2);359
10.16.7;DP Deletion;359
10.16.8;Prostaglandin E2 (PGE2);359
10.16.9;EP Deletion;360
10.16.10;Prostaglandin F2a(PGF2a);360
10.16.11;Concluding Remarks;361
10.16.12;References;361
10.17;Chapter 35: Leukotriene Mediators;366
10.17.1;Introduction;366
10.17.2;5-Lipoxygenase;366
10.17.3;Acknowledgements;370
10.17.4;References;370
10.18;Chapter 36: Sphingosine-1-Phosphate Receptors:An Update;372
10.18.1;Introduction;372
10.18.2;Transactivation of S1PRS;372
10.18.3;S1PRS and the Immune System;373
10.18.4;S1PRS and the Cardiovascular System;374
10.18.5;Concluding Remarks;375
10.18.6;Acknowledgements;375
10.18.7;References;375
11;Section D: Lipid Signaling;380
11.1;Chapter 37: Adenylyl Cyclases;382
11.1.1;Introduction;382
11.1.2;Classification/Structure/Function;382
11.1.3;Endogenous and Exogenous Regulation;385
11.1.4;Roles in Physiology and Diseases;387
11.1.5;Summary;388
11.1.6;References;388
11.2;Chapter 38: Phosphodiesterase Families;392
11.2.1;Introduction;392
11.2.2;The Gene Families;393
11.2.3;Implications of Multiple Gene Families/Splice Variants;394
11.2.4;Altered PDE Expression in Pathological States;395
11.2.5;PDE Inhibitors as Therapeutic Agents;395
11.2.6;Where do we go from here?;396
11.2.7;Acknowledgements;396
11.2.8;References;396
11.3;Chapter 39: cAMP-Dependent Protein Kinase;398
11.3.1;Introduction;398
11.3.2;Catalytic Subunit;398
11.3.3;Structure of the Catalytic Subunit;399
11.3.4;Protein Kinase Inhibitor;402
11.3.5;Regulatory Subunits;402
11.3.6;Holoenzyme Complexes;403
11.3.7;Acknowledgements;404
11.3.8;References;404
11.4;Chapter 40: Cyclic GMP-Dependent Protein Kinase:Targeting and Control of Expression;408
11.4.1;Introduction;408
11.4.2;Cyclic GMP-Dependent Protein Kinase: Structure and Function;408
11.4.3;Targeting of PKG-I in VSMC;409
11.4.4;Role of PKG-I in the Regulation of VSMC Proliferation and Phenotype;410
11.4.5;Regulation of PKG-I Expression;411
11.4.6;Regulation of PFG-I Mrna Levels;411
11.4.7;Final Thoughts;412
11.4.8;References;412
11.5;Chapter 41: Substrates of Cyclic Nucleotide-Dependent Protein Kinases;416
11.5.1;Introduction;416
11.5.2;Classification and Nomenclature;416
11.5.3;Substrates of PKA and PKG;416
11.5.4;Structural and Sequence Features Relevant to Peptide Specificity;417
11.5.5;Conclusions;422
11.5.6;References;422
11.6;Chapter 42: Physiological Substrates ofPKA and PKG;424
11.6.1;Introduction;424
11.6.2;Abundance of PKA and PKG Phosphorylation Sites in the Human Proteome;424
11.6.3;Physiological Substrates;425
11.6.4;Concluding Remarks;438
11.6.5;References;438
11.7;Chapter 43: Inhibitors of Cyclic AMP- and CyclicGMP-Dependent Protein Kinases;442
11.7.1;Introduction;442
11.7.2;Cyclic Nucleotide Binding Site-Targeted Inhibitors;443
11.7.3;ATP Binding Site-Targeted Inhibitors;443
11.7.4;Peptide Binding Site-Targeted Inhibitors;446
11.7.5;Conclusions;447
11.7.6;Acknowledgements;447
11.7.7;References;447
11.8;Chapter 44: AKAP Transduction Units: Contextdependent Assembly of SignalingComplexes;452
11.8.1;Introduction;452
11.8.2;G-Protein Signaling Through AKAP Signaling Complexes;452
11.8.3;Kinase/Phosphatase Signaling Complexes;454
11.8.4;Camp Signaling Units;454
11.8.5;Conclusions and Perspectives;455
11.8.6;Acknowledgements;455
11.8.7;References;456
11.9;Chapter 45: Cyclic Nucleotide Specificity and Cross-Activation of Cyclic Nucleotide Receptors;458
11.9.1;Molecular Basis for CAMP/CGMP Selectivity of PKA and PKG;458
11.9.2;Confounding Factors in Crossactivation Studies;459
11.9.3;Camp Cross-Activation of PKG;459
11.9.4;cGMP Cross-Activation of PKA;460
11.9.5;References;461
12;Section E: G-Proteins;464
12.1;Chapter 46: Signal Transduction by G Proteins: BasicPrinciples, Molecular Diversity, and Structural Basis of Their Actions;466
12.1.1;Introduction;466
12.1.2;Ras, the Prototypic Regulatory Gtpase;467
12.1.3;Heterotrimeric G Proteins;469
12.1.4;Mechanism of G-Protein Activation by Receptors;474
12.1.5;Modulation of Activity by Shortening or Extension of the Active State;479
12.1.6;Future Direction;481
12.1.7;In Memoriam;481
12.1.8;Acknowledgements;481
12.1.9;References;481
12.2;Chapter 47: G-Protein-Coupled Receptors, SignalFidelity, and Cell Transformation;484
12.2.1;Introduction;484
12.2.2;GPCRS and Oncogenesis;485
12.2.3;A Mapk Signaling Network Links Gpcrs to Biological Outcomes;486
12.2.4;ERK Cascade;487
12.2.5;G Protein-Independent Signaling;489
12.2.6;GPCR Effectors are Organized by Scaffolding Molecules;490
12.2.7;AKAPs;492
12.2.8;Conclusion: GPCR Biology Requires Both Signal Integration and Fidelity;493
12.2.9;Acknowledgements;493
12.2.10;References;493
12.3;Chapter 48: Regulation of G Proteins by CovalentModification;498
12.3.1;Introduction;498
12.3.2;N-Terminal Acylation of Ga Subunits;498
12.3.3;C-Terminal Modification of G.;499
12.3.4;Structural and Functional Consequences of Lipid Modifications;499
12.3.5;Lipidation Influences G-Protein Trafficking and Localization;500
12.3.6;Conclusions;501
12.3.7;References;501
12.4;Chapter 49: Signaling Through Gz;504
12.4.1;Introduction;504
12.4.2;General Properties;504
12.4.3;Regulators of GZ Signaling: RGS Proteins;505
12.4.4;Receptors that Couple to GZ;505
12.4.5;Effectors of GZ Signaling;506
12.4.6;Phenotype of GaZ Knockout Mice;506
12.4.7;Concluding Remarks;507
12.4.8;References;507
12.5;Chapter 50: Mono-ADP-Ribosylation ofHeterotrimeric G Proteins;510
12.5.1;Introduction;510
12.5.2;The Mono-ADP-Ribosylation Reaction;510
12.5.3;Bacterial-Toxin-Induced ADP-Ribosylation;511
12.5.4;Endogenous Mono-Adpribosylation;513
12.5.5;Acknowledgements;514
12.5.6;References;514
12.6;Chapter 51: Specificity of G-Protein ß. Dimer Signaling;518
12.6.1;Introduction;518
12.6.2;Diversity of .;518
12.6.3;Application of Genetic Systems for Analysis of . Specificity;519
12.6.4;Conclusions;525
12.6.5;Acknowledgements;525
12.6.6;References;525
12.7;Chapter 52: Reversible Palmitoylation in G ProteinSignaling;528
12.7.1;Introduction;528
12.7.2;Sites of Palmitoylation in Ga and RGS Proteins;528
12.7.3;Activation-Regulated Palmitoylation of Ga;529
12.7.4;Mechanisms of Reversible Palmitoylation;530
12.7.5;Functions of Reversible Palmitoylation;531
12.7.6;Conclusions;532
12.7.7;References;533
12.8;Chapter 53: The Influence of Intracellular Location onFunction of Ras Proteins;536
12.8.1;Introduction;536
12.8.2;Does Location Actually Influence Ras Signaling?;536
12.8.3;Modifications by Endomembrane Enzymes – New Opportunities to Abort Ras Trafficking?;537
12.8.4;Ras Proteins begin their March toward the Cell Surface;537
12.8.5;Ras Activation on ER and Golgi Membranes;538
12.8.6;Destination Cell Surface: Ras Proteins Distribute among Several Plasma Membrane Domains;539
12.8.7;New Destinations – Mitochondria;540
12.8.8;Old Destinations – Endosomes;541
12.8.9;A Reality check – the first Structures of Lipid-Modified Ras on Lipid Membranes;541
12.8.10;References;541
12.9;Chapter 54: Role of R-Ras in Cell Growth;544
12.9.1;Introduction;544
12.9.2;General Properties of R-RAS Proteins: Variations On RAS;544
12.9.3;R-RAS;548
12.9.4;TC21/R-RAS-2;549
12.9.5;M-RAS/R-RAS-3;550
12.9.6;Conclusions;551
12.9.7;Acknowledgements;551
12.9.8;References;551
12.10;Chapter 55: The Ran GTPase: Cellular Roles andRegulation;554
12.10.1;Introduction;554
12.10.2;Structural Analysis of Ran Pathway Components;554
12.10.3;Ran’s Role in Nuclear Transport;556
12.10.4;Ran’s Function in Spindle Assembly;557
12.10.5;Ran’s Function in Cell Cycle Progression;558
12.10.6;Ran’s Role in Nuclear Envelope Dynamics;559
12.10.7;Biological Regulation of Core Ran Pathway Components;559
12.10.8;Conclusions;560
12.10.9;References;560
12.11;Chapter 56: Cdc42 and Its Cellular Functions;564
12.11.1;Introduction;564
12.11.2;Cdc42 Regulates a Variety of Cellular Functions;564
12.11.3;Spatial and Temporal Control of Cdc42 Activity;567
12.11.4;Cooperation Between Cdc42 and other Small Gtpases in Cellular Functions;569
12.11.5;Conclusions;571
12.11.6;References;571
12.12;Chapter 57: Structure of Rho Family Targets;574
12.12.1;Rho Subfamily Protein Structures and Conformational Switch;574
12.12.2;CRIB Proteins;574
12.12.3;Non-CRIB Rac Effectors;579
12.12.4;Rho Effectors;582
12.12.5;ROCK;585
12.12.6;Concluding Remarks;586
12.12.7;References;587
13;Index;590