The GTPase switch appears to be almost as old as life itself, and nature has adapted it to a variety of purposes. This two-volume work surveys the major classes of GTPases, including their role in ensuring accuracy during protein translation, a new look at the trimeric G-protein cycle, the molecular function of ARF in vesicle coating, the emerging role of the dynamin family in vesicle transfer, GTPases which activate GTPases during nascent protein translocation, and the many roles of ras-related proteins in growth, cytoskeletal polymerization, and vesicle transfer. 80 chapters contain much previously unpublished data and, at the rate the extended family of GTPases is growing, it is unlikely that it will again sit for a group portrait such as this. Thus, this could well become the standard reference work.

Inhalt

Section IV: Signal Transduction by Trimeric G Proteins.- A. Cellular Architecture and its Role in Signal Transduction.- 44 G-Proteins Have Properties of Multimeric Proteins: An Explanation for the Role of GTPases in their Dynamic Behavior.- A. Introduction.- B. Theories.- I. Shuttle Theory.- II. Collision-coupling Theory.- III. Disaggregation Theory.- C. Evidence for Multimeric Structures of G-Proteins.- I. Properties in Detergents.- II. Cross-Linking of G-Proteins in Membranes.- III. Glucagon Activation of Multimeric Gs in Hepatic Membranes.- D. Coupling of Receptors to Multimeric G-Proteins.- E. Hydrolysis of GTP Is Fundamental to Signal Transduction Dynamics.- F. Conclusions.- References.- B. G-Protein Coupled Receptors.- 45 The Superfamily: Molecular Modelling.- A. Introduction.- B. General Principles - Modelling Integral Membrane Domains.- I. Summary of Information Available for G-Protein-Coupled Receptor Modelling Studies.- C. Modelling G-Protein-Coupled Receptors from Sequence Alignments.- I. Sequence Comparisons.- II. Fourier Transform Analysis of G-Protein-Coupled Receptor Sequence Alignments.- 1. Prediction of Structural Environments from Sequence Alignments.- 2. Detection of Periodicity and the Discrimination of the Different Sides of the Helix.- 3. Detection of the Ends of the Transmembrane Regions of the Helices.- 4. Summary of Methodology.- 5. Application to G-Protein-Coupled Receptors.- D. Three-Dimensional Models of G-Protein-Coupled Receptors.- I. Construction of G-Protein-Coupled Receptor Models Based on the Fourier Transform Predictions.- II. Analysis of the Models.- References.- 46 The Role of Receptor Kinases and Arrestin-Like Proteins in G-Protein-Linked Receptor Desensitization.- References.- C. Trimeric G-Proteins.- 47 Qualitative and Quantitative Characterization of the Distribution of G-Protein ? Subunits in Mammals.- A. Introduction.- B. Identification of G-Protein ? Subunits.- I. [32P]ADP Ribosylation.- II. Immunological Determination of G-Protein Distribution.- C. Immunological Determination of G-Protein ? Subunit Levels.- I. Quantitative and Relative Intensity Immunoblotting.- II. ELISA.- III. Other Approaches.- D. Asymmetric Distribution of G-Proteins in the Plasma Membrane.- E. Conclusions.- References.- 48 Subunit Interactions of Heterotrimeric G-Proteins.- A. Signalling by ? and ?? Subunits.- I. Effect of Subunit Association on the Guanine Nucleotide Binding and GTPase Activity.- II. Physical Properties of Associated and Dissociated G-Protein Subunits.- III. The ? and ?? Interface.- 1. Analysis by Site-Directed Mutagenesis of Requirments for ? and ?? Interactions.- 2. Analysis of ?? Contact Regions by Cross-Linking.- 3. Probing the ? and ?? Interface with Antibodies.- IV. Does Dissociation of ? and ?? Occur in the Plasma Membrane?.- B. Interaction of ? and ? Subunits.- I. Site of Interaction of ?1 with ?1 and ?2.- C. Specificity of Interaction Between Particular ? and ?? Combinations.- References.- 49 G-Protein ? Subunit Chimeras Reveal Specific Regulatory Domains Encoded in the Primary Sequence.- A. Background.- B. Mutational Analysis of the GDP/GTP Binding Domain.- C. Competitive Inhibitory Mutations.- D. Regulatory Properties of the ?s N Terminus.- E. ?i2/?s Chimeras Reveal the Regulatory Function of the ? Subunit N Terminus.- F. Mutations that Influence GDP Dissociation and GTPase Activity Create Strong Constitutively Active ?s Polypeptides.- G. Sites of ?? Subunit Interactions.- H. Mapping of the ?s Adenylyl Cyclase Activation Domain.- I. Conclusions.- References.- 50 The GTPase Cycle: Transducin.- A. The Retinal cGMP Cascade and Visual Excitation.- B. The Coupling Cycle of Transducin.- C. The Reaction Dynamics of the Transducin Cycle.- I. Transducin Subunit Interaction.- II. Pre-Steady-State Kinetic Analysis of the GTP Hydrolysis Reaction.- III. Quantitative Analysis of the Pre-Steady-State Kinetics.- D. Relationship of GTP Hydrolysis and PDE Deactivation.- E. Regulation of the Transducin Coupling Cycle by Phosducin.- F. Concluding Remarks.- References.- 51 Transcriptional, Posttranscriptional, and Posttranslational Regulation of G-Proteins and Adrenergic Receptors.- A. Introduction.- B. Agonist-Induced Regulation of Transmembrane Signaling.- I. Transcriptional and Posttranscriptional Regulation.- II. Posttranslational Regulation.- C. Cross-Regulation in Transmembrane Signaling.- I. Stimulatory to Inhibitory Adenylyl Cyclase.- II. Inhibitory to Stimulatory Adenylyl Cyclase.- III. Stimulatory Adenylyl Cyclase to Phospholipase C.- IV. Tyrosine Kinase to Stimulatory Adenylyl Cyclase.- D. Permissive Hormone Regulation of Transmembrane Signaling.- E. Perspectives.- References.- 52 G-Protein Subunit Lipidation in Membrane Association and Signaling.- A. Introduction.- B. Myristoylation and Membrane Association of G-Protein ? Subunits.- I. Cotranslational Processing of G-Protein ? Subunits.- II. The Role of Myristoylation in ? Subunit-Membrane Association.- C. Prenylation and Membrane Association of G-Protein ? Subunits.- I. Posttranslational Processing of G-Protein ? Subunits.- II. The Role of Prenylation in ? Subunit-Membrane Association.- 1. Geranylgeranyl-Modified ? Subunits.- 2. Farnesyl-Modified ? Subunits.- D. Future Directions.- References.- 53 Phosphorylation of Heterotrimeric G-Protein.- A. Introduction.- I. Nature of G-Proteins.- II. Modulation of G-Protein Action.- 1. Phosphorylation.- B. Phosphorylation of Heterotrimeric G-proteins in Intact Cells.- I. Hepatocytes.- II. Promonocytic Cell Line U937.- III. Platelets.- 1. Gi-2.- 2. Gz.- IV. Yeast.- V. Dictyostelium.- C. In Vitro Phosphorylation of Isolated Heterotrimeric G-Proteins.- I. Transducin.- II. Gi and Go.- III. Gs.- IV. Unidentified "G-Proteins".- D. Conclusion.- References.- 54 Receptor to Effector Signaling Through G-Proteins: ?? Dimers Join ? Subunits in the World of Higher Eukaryotes.- A. Introduction.- B. ?? Dimers and Adenylyl Cyclase.- I. Hormonal Inhibition of Adenylyl Cyclase and Stimulation of K+ Channels: Controversies that Settled Mostly in Favor of ? Subunits.- II. Conditional and Subtype-Specific Regulation of Adenylyl Cyclase Activity by ?? Dimers.- C. ?? Dimers and Phospholipase C: Subtype-Specific Stimulation of Type ? Phospholipase C by ?? Dimers.- D. ?? Dimers and Receptors: Exquisite Specificity of Receptors for ?? Subtypes.- E. Dual Signaling of Single Receptors: Mediation by One or by Two G-Proteins?.- I. Inhibition of Adenylyl Cyclase and Stimulation of Phospholipase C.- II. Signaling Quality Through Receptor Quantity?.- III. Dual Stimulation of Adenylyl Cyclase and Phospholipase C.- IV. Evidence for Physical Interaction of a Single Receptor with Two Distinct Types of G-Proteins.- F. The Puzzle of the Up-Shifted Dose-Response Curves for Phospholipase C Elicited by Adenylyl Cyclase Stimulating Agonists.- G. Concluding Remarks.- References.- D. Effectors of G-Proteins.- 55 Molecular Diversity of Mammalian Adenylyl Cyclases: Functional Consequences.- A. Introduction.- B. Stimulation and Inhibition of Adenylyl Cyclases.- C. Molecular Diversity of Adenylyl Cyclases.- I. Multiple Families of Adenylyl Cyclases…