Main description:

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ras-related proteins in growth, cytoskeletal polymerization, and vesicle transfer. 80 chapters contain much previously unpublished data and, at the rate the extended family of GTPases is growing, it is unlikely that it will again sit for a group portrait such as this.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.

Contents:

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.- II. Secondary Structure and Topography.- III. Putative Catalytic Sites.- IV. Tissue Distribution of the Various Forms.- D. G-Protein Regulation of Adenylyl Cyclases.- I. Gs-? Regulation.- II. Gi-? Regulation.- III. ?? Regulation.- E. Type-Specific Regulation by Intracellular Ligands.- I. Ca2+/CaM Regulation.- II. Inhibition by Low Concentrations of Ca2+.- III. P-Site Inhibition.- F. Regulation by Protein Phosphorylation.- I. Regulation by Protein Kinase C.- II. Protein Kinase A Regulation: A Component of Heterologous Desensitization.- G. Functional Consequences of Multiple Adenylyl Cyclases.- I. Integration of Multiple Signals.- II. Modulation of Signal Transmission.- References.- 56 The Light-Regulated cGMP Phosphodiesterase of Vertebrate Photoreceptors: Structure and Mechanism of Activation by Gt?.- A. Physiological Role of cGMP Phosphodiesterase in Visual Signaling.- B. Structure.- I. Subunit Composition.- II. Size and Hydrodynamic Properties.- III. Primary Structure.- IV. Posttranslational Modifications.- V. Domain Structures of Subunits.- 1. Catalytic Subunits.- 2. Inhibitory Subunit.- C. Functional Properties.- I. Solubility.- II. Kinetic Properties.- III. Noncatalytic cGMP Binding Sites.- D. Regulation of Catalytic Activity.- I. Inhibition by PDE?.- II. Activation by G-Protein.- 1. Role of Gt?.- 2. Role of Membranes in PDE Activation by Gt?.- 3. Role of PDE? in Activation by Transducin.- 4. Is There Cooperativity in the Action of Gt?-GTP?.- 5. A Role for Noncatalytic cGMP Binding Sites?.- References.- 57 High-Voltage Activated Ca2+ Channel.- A. Introduction.- B. Identified cDNAs of High-Voltage Activated Calcium Channels.- I. The ?1 Subunit.- II. The ?2/? Subunit.- III. The ? Subunit.- IV. The ? Subunit.- C. Structure-Function of the Cloned Calcium Channel Proteins.- I. Expression and Function of the Channel Subunits.- II. The Binding Sites for Calcium Channel Blockers.- III. Phosphorylation of the Channel Proteins.- D. Conclusion.- References.- 58 Phospholipase C-? Isozymes Activated by G?q Members.- References.- 59 Stimulation of Phospholipase C by G-Protein ?? Subunits.- A. Introduction.- B. Stimulation of Soluble Phospholipase C of HL-60 Granulocytes by G-Protein ?? Subunits.- C. Identification of the ??-Sensitive Phospholipase C of HL-60 Granulocytes as PLC?2.- D. Stimulation of PLC?2 by G-Protein ?? Subunits in Intact Cells.- E. Role of ?? Subunits in Mediating Receptor Stimulation of Phospholipase C.- F. Perspectives.- References.- E. Specialized Systems.- 60 Rhodopsin/G-Protein Interaction.- A. Introduction.- B. Interactions of Rhodopsin in the Visual Cascade.- C. Biophysical Monitors of G-Protein Activation.- I. Description of the Monitors.- II. Instrumentation.- III. Application to the Analysis of R*-Gt Interaction.- IV. Preparations.- D. Interactive States of Rhodopsin.- I. Molecular Nature of Metarhodopsin II.- II. Active Forms of Rhodopsin from Alternative Light-Induced Pathways.- III. Activation of Rhodopsin in the Dark.- E. Interactive States of Transducin.- I. Dark Binding.- II. Stable Light Binding with Empty Nucleotide Site.- III. Rhodopsin/G-Protein Interaction with Bound Nucleotides.- F. Mechanism of Transducin Activation.- I. Role of Rhodopsin's Cytoplasmic Loops.- 1. Three Loops Contribute to MII-Gt Interaction.- 2. Loop Mutants: Binding and Activation in MII-Gt Interaction.- II. Dissection of Reaction Steps.- 1. The GDP/MII Switch.- 2. The MII/GTP Switch.- III. Regulation of the Activation Pathway.- G. Conclusion.- References.- 61 Fast Kinetics of G-Protein Function In Vivo.- A. Introduction.- B. Kinetics of Muscarinic K+ Channel Activation.- C. Rapid Desensitization.- D. Kinetics of IK(ACh) Deactivation.- E. Basic Kinetic Model for Membrane-Delimited Effector Activation by a G-Protein.- F. Conclusions.- References.- 62 The Yeast Pheromone Response G-Protein.- A. Introduction.- B. Overview.- C. Gpal, the G? Subunit.- I. Random Mutagenesis.- II. Site-Directed Mutagenesis.- D. Ste4, the G? Subunit.- I. Random Mutagenesis.- II. Site-Directed Mutagenesis.- E. Ste18, the G? Subunit.- I. Random Mutagenesis.- II. Site-Directed Mutagenesis.- F. Conclusions.- References.- 63 Ga Proteins in Drosophila: Structure and Developmental Expression.- A. Introduction.- I. G-Protein-Coupled Signaling in Development.- II. The Drosophila System.- B. G?-Proteins in Drosophila.- I. DGs?.- 1. Gene Structure.- 2. Adult and Embryonic Expression.- 3. Stimulation of Mammalian Adenylyl Cyclase Through DGs?.- II. DGo?.- 1. Gene Structure.- 2. Adult and Embryonic Expression.- III. DGi?.- 1. Gene Structure.- 2. Adult and Embryonic Expression.- IV. DGq?.- 1. Gene Structure.- 2. Adult Expression.- 3. Role in Phototransduction.- V. concertina.- 1. Mutant Phenotype.- 2. Cloning and Gene Structure.- 3. Expression of cta.- C. Summary.- References.- 64 Signal Transduction by G-Proteins in Dictyostelium discoideum.- A. Introduction.- B. Signal Transduction in Dictyostelium.- C. Diversity of G-Proteins in Dictyostelium.- D. Roles of G-Proteins in Signal Transduction Processes.- E. Roles of G-Proteins in Morphogenesis and Differentiation.- F. Conclusions and Perspectives.- References.- 65 Functional Expression of Mammalian Receptors and G-Proteins in Yeast.- A. Introduction.- B. Expression of Mammalian G-Protein-Coupled Receptors.- C. Expression of Mammalian G-Protein Subunits.- I. Physiological Roles of Yeast G-Protein Subunits.- II. Mammalian G? Subunits.- 1. Intact G? Subunits.- 2. Chimeric Yeast/Mammalian G? Subunits.- III. Mammalian G? and G? Subunits.- D. Signaling Between Mammalian Receptors and G-Proteins.- E. Perspectives.- References.- 66 G-Proteins in the Signal Transduction of the Neutrophil.- A. Introduction.- B. Receptor-Mediated PMN Functions.- I. Adherence.- II. Chemotaxis.- III. Phagocytosis and Bactericidal Activity.- IV. Regulatory Receptors.- C. G-Protein-Coupled Receptors.- I. Chemoattractant Receptors.- II. Purinergic Receptors.- III. Other PMN Receptors.- D. Regulation of Neutrophil Responses.- I. Priming.- II. Desensitization.- References.- 67 Hormonal Regulation of Phospholipid Metabolism via G-Proteins: Phosphoinositide Phospholipase C and Phosphatidylcholine Phospholipase D.- A. Introduction.- B. Identification of the G-Proteins Regulating PtdInsP2 Phospholipase C.- C. Coupling of G-Proteins to Ca2+-Mobilizing Receptors.- D. Specificity of Phosphoinositide Phospholipase C Linked to Gq and G11.- E. Mechanisms of Agonist-Stimulated Phosphatidylcholine Breakdown.- F. Summary.- References.- 68 Hormonal Regulation of Phospholipid Metabolism via G-proteins II: PLA2 and Inhibitory Regulation of PLC.- A. Introduction.- B. Modulation of PLA2.- I. Molecular Forms of PLA2.- II. G-Protein-Mediated Activation of PLA2.- III. Molecular Aspects.- IV. Inhibitory Regulation of PLA2.- C. Activity of PLA2 in ras-Transformed Cells.- D. Inhibitory Regulation of PLC.- I. Molecular Aspects.- E. Conclusion.- References.- 69 G-Protein Regulation of Phospholipase C in the Turkey Erythrocyte.- A. Introduction.- B. Properties of P2Y Purinergic Receptor and G-Protein-Regulated PLC in Turkey Erythrocytes.- I. Initial Observations.- II. Kinetics of Activation of PLC by P2Y Purinergic Receptor Agonists and Guanine Nucleotides.- C. Identification, Purification, and Primary Structure of the Protein Components of the Turkey Erythrocyte Inositol Lipid-Dependent Signaling System.- I. G-Protein-Regulated PLC.- 1. Purification and Properties of a G-Protein-Regulated PLC from Turkey Erythrocytes.- 2. Receptor and G-Protein Regulation of the Purified Turkey Erythrocyte PLC.- II. G-Protein Activators of PLC.- 1. Purification and Properties of the Turkey Erythrocyte PLC-Activating G-Protein.- 2. cDNA Sequence of the Turkey Erythrocyte PLC-Activating G-Protein and its Relationship to Mammalian G-Protein ? Subunits.- D. Concluding Comments.- References.- 70 Hormonal Inhibition of Adenylyl Cyclase by ?i and?? ?i or ?? ?i and/or ??.- A. Introduction.- B. Mechanism(s) Mediating Inhibition of Adenylyl Cyclase.- I. Direct Inhibition of Adenylyl Cyclase by ?i.- II. Indirect Inhibition of Adenylyl Cyclase by ?? Suppression of ?s Activation.- III. Direct Inhibition of Adenylyl Cyclase by ??.- C. Current View of Inhibition of Adenylyl Cyclase.- I. The Mechanism of Inhibition of Adenylyl Cyclase in S49 Cells.- II. Significance and Predications of Multiple Mechanism fo Inhibition.- III. Unresolved Structural and Functional Issues about G-proteins Affecting the Mechanism(s) Mediating Hormone Inhibition of Adenylyl Cyclase.- D. Conclusion.- References.- 71 Neurobiology of Go.- A. Introduction.- B. Gene Structure of Go? in Vertebrates and Invertebrates.- I. Gene Structure and Transcription in Vertebrates.- II. Gene Structure and Transcription in Invertebrates.- C. Cellular Expression of Go in Excitable Cells and Its Regulation.- I. Cellular and Subcellular Distribution.- 1. Neurons.- 2. Nonneuronal Cells.- II. Control of Go, Go1, and Go2 Expression During Neuronal Differentiation.- D. Neurotransmitter Receptors Coupled to Go and Their Inhibitory Effects on Voltage-Sensitive Ca2+ Channels.- I. Nature of Receptors.- 1. Reconstitution of Resolved Receptors and Go-Proteins.- 2. Reconstitution of Receptor Coupling to VSCC with Go-Protein in PTX-Treated Cells.- 3. Stimulation of Go Photolabeling with [?32-P]GTP Azidoanilide by Neurotransmitters.- 4. Intracellular Injections of G-protein Antibodies and of Antisense Oligonucleotides Complementary to G-Protein or DNA Sequences To Demonstrate the Specificity of the Negative Coupling Between Receptors and VSCC via Go.- 5. Immunoprecipitation of Receptor-Go Complexes with Anti-Go Antibodies and Anti-receptor Antibodies.- II. Nature of VSCC Inhibited by Go.- III. Colocalization of Go and L-Type VSCC in T-Tubule.- IV. Conclusions.- E. General Conclusion.- References.- 72 Involvement of Pertussis-Toxin-Sensitive G-Proteins in the Modulation of Ca2+ Channels by Hormones and Neurotransmitters.- A. Introduction.- B. Inhibitory Modulation of Voltage-Dependent Ca2+ Channels.- I. Occurrence; Physiological Significance.- II. Effects of Receptor Agonists, Pertussis Toxin, and Guanine Nucleotides.- III. Types of Ca2+ Channels Affected by Inhibitory Receptor Agonists.- IV. Mechanistic Aspects.- 1. Cyclic Nucleotides.- 2. Protein Kinase C and Fatty Acids.- 3. Evidence for a Membrane-Delimited Pathway.- V. Identification of the Involved G-Protein.- 1. Occurrence of Go.- 2. Reconstitution Experiments with Native and Recombinant G-Proteins; Transfected Cells.- 3. Antibodies.- 4. Go-Activating Receptors.- 5. Antisense Oligonucleotides.- C. Stimulatory Modulation of Voltage-Dependent Ca2+ Channels.- I. Occurrence; Physiological Significance.- II. Effects of Pertussis Toxin and Guanine Nucleotides.- III. Types of Ca2+ Currents Affected by Stimulatory Receptor Agonists.- IV. Mechanistic Aspects.- V. Identity of the G-Protein Involved.- D. Conclusion.- References.- 73 Regulation of Cell Growth and Proliferation by Go.- A. Introduction.- B. The Go-Protein.- C. The Go-Protein and Cell Cycle Regulation in the Xenopus Oocyte.- D. Regulation of Oocyte Maturation by Multiple Pathways.- E. Proliferation of Mammalian Cells by Activated Go.- F. Specificity of Transformation by Signaling Through G-Protein Pathways.- G. Desensitization and Growth Signaling Through G-Protein Pathways.- References.- 74 Role of Nucleoside Diphosphate Kinase in G-Protein Action.- A. Introduction.- B. General Model of Membrane Signaling Systems Involving G-Proteins.- C. Role of NDP Kinase in Membrane Signaling Systems.- I. Evaluation of the Effect of GDP in Comparison with GTP.- II. Role of mNDP Kinase in Signal Transduction.- III. Comparison Between Hormone and Cholera Toxin Actions.- IV. Interaction Between mNDP Kinase and Gs and Its Regulation.- V. Regulatory Mechanism of G-Protein by NDP Kinase.- VI. Physiological Relevance of G-Protein Regulation by mNDP Kinase.- D. Properties of NDP Kinases and Their Structure.- E. Novel Roles of NDP Kinases in Cellular Functions.- F. Concluding Remarks.- References.- 75 G-Protein Regulation of Cardiac K+ Channels.- A. Introduction.- B. Involvement of G-Protein in Muscarinic Activation of the KACh Channel.- C. Physiological Mode of G-Protein Activation of the KACh Channel.- D. Effects of G-Protein Subunits on the Cardiac KACh Channel.- I. Comparison Between the Regulation of Adenylyl Cyclase Activity and the KACh Channel Activity by Purified G-Protein Subunits.- II. Effects of G?? on the KACh Channel.- 1. Voltage-Dependent Properties of the G??-Activated KACh Channel.- 2. Concentration Dependence of G?? Activation of the KACh Channel.- 3. Specificitiy of G?? Activation of the KACh Channel.- 4. G?? Activation of the KACh Channel Is Not Mediated by Phospholipase A2.- 5. Antibody 4A Does Not Inhibit the Interaction Between GK and the KACh Channel.- III. Effects of G-Protein on the ATP-Sensitive K Channel.- E. Stimulatory Modulation of the GK-Gated Cardiac KACh Channel.- I. Arachidonic Acid and Its Metabolites.- II. Phosphorylation.- III. NDP-Kinase.- IV. Intracellular Chloride.- F. Conclusion.- References.- 76 Modulation of K+ Channels by G-Proteins.- A. Direct Regulation of Ionic Channels by G-Proteins.- I. The Inwardly Rectifying "Muscarinic" K+ Channel.- 1. Experiments Leading to the Discovery of G-Protein Gating.- 2. Direct Stimulation by hRBC Gi and Its ? Subunit.- 3. Properties of the Gi-stimulated K+ Channel.- 4. Identity of the Gk that Gates the Muscarinic-Type K+ Channels.- II. The ATP-Sensitive K+ Channel: A Second Gi-Gated K+ Channel.- 1. General Properties of the ATP-Sensitive K+ Channel/ Sulfonyliurea Receptor Complex.- 2. Identity of G-proteins that Regulate the ATP-Sensitive K+ Channel.- III. G-Protein Gating as a Tool To Discover Novel Ionic Channels: Neuronal Go-Gated K+ Channels.- B. Effect of ?? Dimers: Inhibition versus Stimulation of the Muscarinic K+ Channel - A Persisting Controversy.- C. Conclusions.- References.- 77 ATP-Sensitive K+ Channel: Properties, Occurrence, Role in Regulation of Insulin Secretion.- A. Introduction.- B. Biophysical Properties.- C. Regulation of the KATP Channel.- I. Inhibition by Intracellular Nucleotides.- II. Activation by Intracellular Nucleoside Diphosphates.- III. Activation by Intracellular MgATP.- IV. Activation by G-Proteins.- V. Inhibition by G-Proteins.- VI. Inhibition by Drugs.- VII. Activation by Drugs.- VIII. Characteristics of the Sulfonylurea Receptor.- D. Role of the KATP- Channel in Regulation of Insulin Secretion.- References.- 78 Modulation of Maxi-Calcium-Activated K Channels: Role of Ligands, Phosphorylation, and G-Proteins.- A. Introduction.- B. Mechanisms of Metabolic Regulation of Maxi-KCa Channels.- I. Ligand Modulation.- 1. Arachidonic Acid.- 2. Angiotensin II and Thromboxane A2.- 3. Guanine Nucleotides.- 4. Intracellular pH.- II. Phosphorylation/Dephosphorylation Cycles.- 1. Pituitary Maxi-KCa Channels.- 2. Brain Maxi-KCa Channels.- 3. Colonic Maxi-KCa Channels.- 4. Myometrial Maxi-KCa Channels.- III. G-Protein Gating.- 1. Muscarinic Regulation.- 2. Adrenergic Stimulation.- C. Conclusions.- References.- 79 Regulation of the Endosomal Proton Translocating ATPase (H+-ATPase) and Endosomal Acidification by G-Proteins.- A. Introduction.- B. Endocytosis.- I. General.- II. The Kidney.- C. Endosomal Acidification.- I. Potential Role for G-Proteins in Endosomal Acidification.- II. Effects of G-Proteins on Endosomal Acidification.- D. Conclusions.- References.- 80 cAMP-Independent Regulation of Adipocyte Glucose Transport Activity and Other Metabolic Processes by a Complex of Receptors and their Associated G-Proteins.- A. Introduction.- B. Lack of a Relationship Between cAMP and Glucose Transporter Activity.- C. G-Proteins in Glucose Transporter Regulation.- D. How Do G-Proteins Mediate Glucose Transporter Activity?.- E. Other RSGS- and RiGiMediated Processes in Adipocytes.- F. Conclusions and Speculations.- References.