G Proteins

G Proteins

2nd Edition - December 28, 1989

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  • Editor: Ravi Iyengar
  • eBook ISBN: 9780323161404

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G Proteins is an introduction to one class of systems used for signal transduction at the cell surface, with emphasis on its utilization of a heterotrimeric GTP-binding protein (G protein) to mediate the transfer of information across the plasma membrane, from receptor to effector. Topics covered include the structure and function of G-protein α chains, ADP-ribosylation factor of adenylyl cyclase, and G protein-mediated effects on ionic channels. The organization of genes coding for G-protein α subunits in higher and lower eukaryotes is also discussed. This book is comprised of 25 chapters and begins with an overview of G proteins and their role in signal transduction. The next section focuses on the structural aspects of G proteins, with substantial emphasis on ? subunits. The mechanism of G protein coupling to effector systems is also considered, using the hormone-regulated adenylyl cyclase and light-regulated cGMP phosphodiesterase as models. Subsequent chapters deal with receptors and effector systems, together with the cellular functions that may be regulated by heterotrimeric G proteins. In particular, the interaction of insulin with G proteins is discussed, along with receptor regulation of cell calcium and phospholipase C activity. This monograph should be useful to students and scientists interested in G proteins.

Table of Contents

  • Contributors


    1. Overview

    I Structural Aspects

    2. Structure and Function of G-Protein α Chains

    I. Introduction

    II. Structure of G-Protein α Chains

    III. Summary and Prospects


    3. Structure and Function of G-Protein βγ Subunit

    I. Structure of βγ Subunit

    II. Distribution of β Subunits

    III. Membrane Association of βγ

    IV. Functional Regions of βγ Subunits

    V. Effect of βγ Subunit on Function of α Subunit

    VI. Interaction of βγ with Effectors

    VII. Conclusion


    4. Organization of Genes Coding for G-Protein α Subunits in Higher and Lower Eukaryotes

    I. Isolation of cDNA Clones for G-Protein α Subunits from Mammalian Cells

    II. Isolation of Human Gα Genes

    III. Structure of Human Gsα Gene and Generation of Four Gsα cDNAs by Alternative Splicing

    IV. Human Genes for Giα Subtypes

    V. Organization of Human Ga Genes

    VI. Conservation of Primary Structure of Each Ga among Mammalian Species

    VII. G Proteins from Saccharomyces cerevisiae

    VIII. Comparison of Amino Acid Sequences of Yeast GP1α and GP2α with Those of Rat Brain Giα and Goα


    5. Structural, Immunobiological, and Functional Characterization of Guanine Nucleotide-Binding Protein Go

    I. Introduction

    II. Purification and Biophysical and Biochemical Characterizations of Brain Go Protein

    III. Structure of Goα

    IV. Production and Specificity of Anti-Goα Antibodies

    V. Tissue Distributions of Goα Protein and mRNA Coding for Goα

    VI. Cellular and Subcellular Immunolocalization of Goα

    VII. Roles of Go


    6. Immunologic Probes for Heterotrimeric GTP-Binding Proteins

    I. Introduction

    II. Immunochemical Studies of G-Protein Subunit Structure

    III. Immunochemical Studies of G-Protein Function

    IV. Quantitation and Distribution of G Proteins


    Part II Coupling

    7. Adenylyl Cyclase and Its Regulation by Gs

    I. Introduction

    II. Regulation of Adenylyl Cyclase by Gs

    III. Cloning and Characterization of Products of αs Gene

    IV. Adenylyl Cyclase: Molecular Characterization

    V. Desensitization of Adenylyl Cyclase

    VI. Editor's Comments (by Ravi Iyengar)


    8. Participation of Guanine Nucleotide-Binding Protein Cascade in Activation of Adenylyl Cyclase by Cholera Toxin (Choleragen)

    I. Introduction

    II. ADP-Ribosyltransferase and NAD+ Glycohydrolase (NADase) Activities of Choleragen

    III. Effect of ADP-Ribosylation Factor on Enzymatic Activities of Choleragen

    IV. Similarities between Choleragen and Escherichia coli Heat-Labile Enterotoxin

    V. Evidence for ADP-Ribosylation Cycle Endogenous to Animal Cells


    9. ADP-Ribosylation Factor of Adenylyl Cyclase: A 21-kDa GTP-Binding Protein

    I. Introduction

    II. Role of ADP-Ribosylation Factor in Cholera Toxin Action

    III. Cholera Toxin as Probe for Gs

    IV. ADP-Ribosylation Factor as GTP-Binding Protein

    V. Cellular Localization of ADP-Ribosylation Factor

    VI. Structure of ADP-Ribosylation Factor

    VII. Comparison to Other GTP-Binding Proteins

    VIII. Future Directions


    10. Transducin, Rhodopsin, and 3',5'-Cyclic GMP Phosphodiesterase: Typical G Protein-Mediated Transduction System

    I. Introduction: Rhodopsin-Transducin -3',5'-Cyclic GMP Phosphodiesterase Cascade as Model for G Protein-Mediated Processes

    II. "Inactive" Τα-GDP-Tßγ Holoenzyme: Membrane Attachment, Requirement for Magnesium, Absence of Precoupling

    III. Transducin-Photoexcited Rhodopsin Interaction

    IV. Activated Forms of Τα: Τα-GTP, Τα-GTPγS and Τα-GDP-A1F

    V. Transducin and 3',5'-Cyclic GMP Phosphodiesterase

    VI. Hydrolysis of GTP in Τα and Inactivation of Transducin

    VII. Conclusion


    11. G Protein-Mediated Effects on Ionic Channels

    I. Direct G-Protein Gating of K+ Channels

    II. Direct G-Protein Gating of Ca2+ Channels

    III. G-Protein Subunits Mediating Direct Ionic Channel Gating

    IV. Indirect G-Protein Gating of Ionic Channels

    V. Conclusions


    12. Receptor-Effector Coupling by Pertussis Toxin Substrates: Studies with Recombinant and Native G-Protein a Subunits

    I. Introduction

    II. Pertussis Toxin: Structure and Conditions of Toxin-Catalyzed ADP-Ribosylation

    III. What is Gi and What it Means Now

    IV. Bacterial Expression of a Subunits

    V. Recombinant a Subunits and Effector Functions

    VI. Identification of Native Gi: Immunoblotting Using Sequence-Specific Antisera

    VII. G-Protein Purification: Resolution of Closely Related G Proteins

    VIII. Effector Functions of a Subunits: Recombinant versus Native Proteins

    IX. Conclusions and Future Directions


    13. Structure and Function of Adrenergic Receptors: Models for Understanding G-Protein-Coupled Receptors

    I. Components of Hormone-Sensitive Adenylyl Cyclase Systems

    II. Structure of Adrenergic Receptors

    III. Functional Domains

    IV. Ligand Binding

    V. Receptor-G Protein Coupling

    VI. Regulation of Receptor Function by Covalent Modifications


    14. Muscarinic Receptors and Their Interactions with G Proteins

    I. Introduction

    II. Muscarinic Receptors and Phosphoinositide Metabolism

    III. Muscarinic Receptors and Ion Channels

    IV. Subtypes of Muscarinic Receptors

    V. Molecular Cloning and Structure of mAChR


    Part III Systems Regulated by G Proteins

    15. G Protein- and Protein Kinase C-Mediated Regulation of Voltage-Dependent Calcium Channels

    I. Introduction

    II. Transmitters, G Proteins, and Second Messenger Systems Associated with Inhibition of Calcium Current

    III. Involvement of Protein Kinase C in Calcium Channel Modulation

    IV. Conclusions


    16. Receptor-Ion Channel Coupling through G Proteins

    I. Introduction

    II. G Protein-Controlled K+ Current in Cardiac Cells

    III. G-Protein Control of Ca2+ Current in Neuronal and Endocrine Cells

    IV. Conclusions


    17. Signal Transduction in Olfaction and Tast

    I. Introduction

    II. Receptor Hypothesis

    III. G Proteins Identified in Chemosensory Membranes

    IV. Second Messengers in Chemosensory Transduction

    V. Editor's Comments (by Ravi Iyengar)


    18. Phosphatidylinositol Phospholipase C

    I. Action of Phospholipase C

    II. Purification of Phospholipase C

    III. Regulation of Phospholipase C


    19. Receptor Modulation of Phospholipase C Activity

    I. Introduction

    II. Studies in Cell-Free Systems

    III. Characterization of G Protein-Phospholipase C Complex

    IV. Future Directions


    20. Xenopus Oocyte as Model System to Study Receptor Coupling to Phospholipase C

    I. Introduction

    II. Oocyte Morphology, Membrane Properties, and Electrophysiology

    III. Receptor-Activated Inositol 1,4,5-Trisphosphate-Mediated Cl-Conductance in Xenopus Oocyte: Native Muscarinic Receptor, Transplanted Receptors, and General Pathway

    IV. Xenopus Oocyte and G Proteins

    V. Summary


    21. Receptor Regulation of Cell Calcium

    I. Introduction

    II. Receptors Linked to Phospholipase C

    III. Receptors Not Linked to Phospholipase C


    22. Insulin and Its Interaction with G Proteins

    I. Introduction

    II. Structure of Insulin Receptor

    III. Action of Insulin on Cyclic AMP Metabolism

    IV. Inhibition of Adenylyl Cyclase

    V. Stimulation of Distinct GTPase Activity in Human Platelets by Insulin

    VI. Phosphorylation of Defined GTP-Binding Proteins by Human Insulin Receptor

    VII. Concluding Remarks


    23. G Proteins in Growth Factor Action

    I. Introduction

    II. Chinese Hamster Lung Fibroblasts: A Model System to Analyze Growth Factor Action

    III. Mechanisms of Growth-Factor Signal Transduction

    IV. Evidence for Two G Proteins Involved in Initiation of Growth

    V. ras and Growth-Factor Signaling Pathways

    VI. Conclusions

    VII. Editor's Comments (by Ravi Iyengar)


    24. G Proteins in Yeast Saccharomyces cerevisiae

    I. Introduction

    II. Pheromone Response and Mating in Yeast

    III. Identification of SCG1 (GPA1), a Gα Homolog

    IV. Mutations in SCG1 Indicating a Role for SCG1 in Pheromone Response Pathway

    V. Rat Gα Subunits Complementing scg1 Growth Defect

    VI. Identification of β and γ Subunits Involved in Pheromone Response

    VII. Epistatic Relationships

    VIII. Models for Mechanism of Pheromone Response

    IX. Identification of Second Gα Homolog (GPA2)

    X. Perspectives


    25. GTP-Binding Proteins and Exocytotic Secretion

    I. Ca2+: Secundus inter pares in Exocytotic Secretion

    II. Exocytotic Mechanisms

    III. G Proteins and Stimulus-Secretion Coupling

    IV. Role of G Proteins in Control of Secretion

    V. GP and GE Act in Series to Control Exocytosis in Mast Cells

    VI. Modulation of Exocytosis by ATP

    VII. G-Protein Regulation of Degranulation in Single Cells

    VIII. Conclusion



Product details

  • No. of pages: 670
  • Language: English
  • Copyright: © Academic Press 1989
  • Published: December 28, 1989
  • Imprint: Academic Press
  • eBook ISBN: 9780323161404

About the Editor

Ravi Iyengar

Affiliations and Expertise

Mount Sinai School of Medicine, New York, U.S.A.

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