G Proteins - 2nd Edition - ISBN: 9780123774507, 9780323161404

G Proteins

2nd Edition

Editors: Ravi Iyengar
eBook ISBN: 9780323161404
Imprint: Academic Press
Published Date: 28th December 1989
Page Count: 670
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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



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




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© Academic Press 1990
Academic Press
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About the Editor

Ravi Iyengar

Affiliations and Expertise

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

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