Mechanisms of receptor regulation
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書誌事項
Mechanisms of receptor regulation
（New horizons in therapeutics）
Plenum Press, c1985
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"Summarizes the proceedings of the Second Smith, Kline & French Research Symposium on New Horizons in Therapeutics, held in Philadelphia in 1984"--Pref
Includes bibliographies and index
内容説明・目次
内容説明
It is less than 80 years since John Newport Langley first proposed the role of "receptive substances" as the site of drug action from his obser- vations on the effects of nicotine and curare at the myoneural junction. The many advances in our understanding of receptor biology that have occurred during the intervening period mirror the extraordinary growth of knowledge in the biological sciences and in cell and molecular biology in particular. Receptor biology, in common with many other topics in contemporary biology, is on the threshold of a transition from being a descriptive, phenomenological discipline to one in which underlying mechanisms and regulatory principles can be defined with increasing pre- cision. This change, together with the evolution of powerful analytical techniques and timely convergence of ideas from a number of previously separate fields of inquiry, is generating an increasingly unified theoretical and experimental framework for the study of receptor function. These themes, and the mood of anticipation that a real understanding of receptor function in health and disease is emerging, are reflected in in this volume, which summarizes the proceedings of the Sec- the papers ond Smith Kline & French Research Symposium on New Horizons in Therapeutics held in Philadelphia in 1984.
目次
1 Receptor Regulation: Problems and Perspectives.- 1. Introduction.- 2. Receptor Regulation.- 3. Insulin Receptor Studies.- 4. Conclusion.- References.- 2 Patterns in Receptor Behavior and Function.- 1. Introduction.- 2. Class I Receptors.- 3. Class II Receptors.- 4. Recycling and the Endosome.- 5. Role of the Endosome in Regulating Cell Surface Area.- References.- 3 The Membrane Receptors of Epidermal Growth Factor: Structural and Functional Studies.- 1. Introduction.- 2. Results.- 2.1. Purification of EGF Receptor by Immunoaffinity Chromatography.- 2.2. Structural Domains on EGF Receptor: Analysis with Immunologic Probes.- 3. Discussion.- 4. Concluding Remarks.- References.- 4 The Insulin Receptor as a Tyrosine-Specific Protein Kinase.- 1. Introduction.- 2. Development of a Monoclonal Antibody to the Human Placental Insulin Receptor.- 3. Purification of the Insulin-Dependent Protein Kinase from Human Placenta.- 4. Properties of the Purified Human Placental Insulin-Dependent Protein Kinase.- 5. Substrates for the Insulin-Dependent Protein Kinase.- 5.1. Peptides.- 5.2. Proteins.- 6. Properties of the Phosphoreceptor: Consequences of Reversible Autophosphorylation.- 7. Insulin-Promoted Phosphorylation in 3T3-L1 Adipocytes.- 8. Concluding Remarks.- References.- 5 Signal Transduction in Biological Membranes.- 1. Information Processing: Some Generalities.- 2. Transduction and the Adenylate Cyclase System.- 3. GTP Binding Proteins: A Family of Membrane Regulatory Proteins.- 4. Organization of Receptors and Transduction Elements in Membranes.- 5. Summary.- References.- 6 Receptor-Controlled Phosphatidylinositol 4,5-Bisphosphate Hydrolysis in the Control of Rapid Receptor-Mediated Cellular Responses and of Cellular Proliferation.- 1. Introduction.- 2. "V1 Vasopressin Receptors": Receptors for Hormone or Neurotransmitter.- 3. Phosphatidylinositol 4,5-Bisphosphate Hydrolysis as a Coupling Reaction in Receptor-Mediated Signaling.- 4. Stimulated Inositol Lipid Metabolism and Cell Proliferation.- References.- 7 Requirements for Steroid Hormone Action in Eucaryotic Cells.- 1. Introduction.- 2. Receptors for Progesterone.- 3. Postreceptor Specificity.- 4. Induction of Transcription.- 5. Tissue-Specific Factors.- 6. Role of the Nuclear Matrix.- 7. Conclusions.- References.- 8 Inositol Trisphosphate and Diacylglycerol as Intracellular Second Messengers.- 1. Introduction.- 2. Formation of Diacylglycerol and Inositol Trisphosphate.- 3. Removal of Diacylglycerol and Inositol Trisphosphate.- 4. Mode of Action of Diacylglycerol and Inositol Trisphosphate.- 5. Functional Interactions between Diacylglycerol and Calcium.- 6. Oncogenes and Phosphoinositide Metabolism.- 7. Phosphoinositide Levels and Receptor Sensitivity.- References.- 9 Ionic Signal Transduction by Growth Factors.- 1. Introduction.- 2. Monovalent Ions in Growth Factor Action.- 2.1. Rapid Electrical Events.- 2.2. The Na+-K+ Pump and Na+-H+ Exchange.- 2.3. Changes in Cytoplasmic Ph.- 2.4. Metabolic Effects of a Rise in pHi.- 3. Calcium Mobilization by Growth Factors.- 4. Concluding Remarks.- References.- 10 Guanine-Nucleotide-Binding Regulatory Proteins: Membrane-Bound Information Transducers.- 1. Introduction.- 2. The G-Protein Family.- 3. Regulation of Adenylate Cyclase Activity by Gs and Gi.- 4. Speculations.- References.- 11 Role of Cyclic-AMP-Dependent Protein Kinase in the Regulation of Cellular Processes.- 1. Criteria for Evaluating the Role of Protein Phosphorylation in Cyclic-AMP-Mediated Processes.- 2. Additional Approaches.- 2.1. Measurement of the Activity of Cyclic-AMP-Dependent Protein Kinases in Vivo.- 2.2. Introduction of Kinase Subunits into Cells.- 2.3. Stoichiometry of Protein Phosphorylations.- 3. Selected Examples of Cyclic-AMP-Mediated Protein Phosphorylation.- 3.1. Skeletal Muscle Phosphorylase Kinase.- 3.2. Cyclic-AMP-Dependent Phosphorylation of Smooth Muscle Myosin Light-Chain Kinase.- 3.3. Activation of Tyrosine Hydroxylase by Neuronal Depolarization.- 3.4. Cyclic-AMP-Dependent Protein Phosphorylation and Nuclear Events.- 4. Conclusions.- References.- 12 The Homogeneity and Discreteness of Membrane Domains.- 1. Introduction.- 2. Membrane Traffic and Cytoplasmic Compartmentalization.- 3. Endocytosis and the Vacuolar Apparatus.- 4. Membrane Recycling within the Vacuolar Apparatus.- 5. The Synthetic Compartment.- 6. Surveillance and Reconstitution.- 7. The Generation of Vesicles: Membrane Faces.- 8. Membrane Coats and the Generation of Vesicles.- 9. Other Pathways.- References.- 13 Internalization and Processing of Peptide Hormone Receptors.- 1. Receptor-Mediated Endocytosis.- 2. Endocytosis of Hormones.- 3. Acidic Nature of Endosomal Compartments: Consequences.- 4. Endocytosis and Hormone Receptor Activation.- 5. Other Mechanisms in Receptor Activation.- 6. Receptor Tyrosine Kinase Activity.- 7. Protein Kinase C, Phorbol Esters, Polyinositides, and Receptors.- 8. Receptor Aggregation and Dimerization.- 9. Conclusions.- References.- 14 Sorting and Recycling of Cell Surface Receptors and Endocytosed Ligands: The Asialoglycoprotein and Transferrin Receptors.- 1. Summary.- 2. Introduction.- 3. The Asialoglycoprotein Receptor.- 3.1. Recycling of the Asialoglycoprotein Receptor: Biochemical Evidence.- 3.2. Recycling of the Asialoglycoprotein Receptor: Immunoelectron Microscopy during Receptor-Mediated Endocytosis.- 4. The Transferrin Receptor.- 4.1. General Properties.- 4.2. The Fate of the Transferrin Polypeptide and Iron during a Single Cycle of Endocytosis.- 4.3. pH and the Recycling of Transferrin and the Transferrin Receptor during Receptor-Mediated Endocytosis.- 4.4. Determination of the Cycle Time of Transferrin Receptor.- 4.5. Are Cell Surface Receptors Internalized and Recycled Independently?.- 5. Concluding Remarks.- References.- 15 The Nicotinic Acetylcholine Receptor: Its Structure, Multiple Binding Sites, and Cation Transport Properties.- 1. Introduction.- 2. Subunits of Torpedo AcChR.- 3. Nonequivalence of the Two ?-Subunits.- 4. The AcChR is a Transmembrane Protein.- 5. Exposure of AcChR Subunits to the Lipid Bilayer.- 6. The AcChR from Torpedo as a Model for Other Nicotinic AcChRs.- 7. Structure of Mammalian Muscle AcChR.- 8. The AcChR as a Cation Channel.- 9. Agonist Binding to Torpedo AcChR.- 10. The Mechanism of Agonist Binding to the Low-Affinity Site.- 11. Conformational Coupling between Agonist Binding and Channel Opening.- 12. Independent Pathways for Channel Activation and Desensitization.- 13. Conclusion.- References.- 16 Adenylate-Cyclase-Coupled (3-Adrenergic Receptors: Biochemical Mechanisms of Desensitization.- 1. Introduction.- 2. Mechanisms of Desensitization of the Adenylate Cyclase Response to Catecholamines.- 2.1. Physical Sequestration of ss-Adrenergic Receptors: The Frog Erythrocyte Model System.- 2.2. Covalent Modification of the Receptors: The Turkey Erythrocyte Model System.- 3. Summary.- References.- 17 Control of Receptor Function by Homologous and Heterologous Ligands.- 1. Introduction.- 1.1. Defining Receptors as Heterogeneous Pharmacological Entities.- 1.2. Receptors as Dynamic Cell Surface Entities.- 2. Ligand-Mediated Receptor Control.- 2.1. Levels of Control of Receptor Function.- 2.2. Levels of Control of Receptor Number.- 2.3. Homospecific versus Heterospecific Receptor Regulation.- 3. Mechanisms of Receptor Regulation.- 3.1. Receptor Phosphorylation.- 3.2. Disulfide-Sulfhydryl Exchange Reactions.- 3.3. Receptor Proteolysis.- 3.4. Change in Membrane Potential.- 3.5. Changes in Receptor Distribution.- 3.6. Allosteric Interactions.- 3.7. Changes in Lipid Environment.- 4. Consequences of Ligand-Modulated Receptor Regulation.- 4.1. Pathophysiological Implications.- 4.2. Therapeutic Implications.- 5. Summary.- References.- 18 Ligand-Receptor Interactions at the Cell Surface.- 1. Introduction.- 1.1. Defining a Receptor.- 1.2. Receptors versus Acceptors.- 1.3. Distinguishing Receptor from Nonreceptor Interactions.- 2. Receptor Dynamics and Hormone Action.- 2.1. The Mobile or Floating Receptor Paradigm.- 2.2. Receptor Microclustering, Aggregation, Ligand Internalization, and Hormone Action.- 2.3. Receptor Regulation.- 3. Kinetics of Ligand Binding.- 3.1. Binding Kinetics for a Simplified Model.- 3.2. Departures from the Simple Model of Ligand Binding.- 4. Receptor Structure and Molecular Models for Hormone-Mediated Cell Activation.- References.- 19 Unique Tumor-Specific Antigens as Altered Cell-Surface Receptors.- 1. Introduction and Definition of Unique Tumor-Specific Antigens.- 2. Appearance of Unique Tumor-Specific Antigens as a Result of Carcinogen Exposure.- 3. Possible Relationship of Unique Tumor Antigens to the Malignant Phenotype.- 4. Three Gene Families Implicated in the Generation of Unique Tumor Antigens.- 5. Strong Unique Tumor-Specific Antigens on Potentially Malignant Cells.- 6. Multiplicity of Unique Tumor-Specific Antigens on a Single Tumor Cell.- 7. Exploratioin of the Molecular Nature of Unique Tumor- Specific Antigens on a UV Induced Tumor.- 8. Possible Effects of Altered MHC Molecules on Various Receptor Functions at the Cancer Cell Surface.- References.- 20 Mechanisms That Regulate Membrane Growth Factor Receptors.- 1. Introduction.- 2. Isoproterssssenol Action on the Insulin Receptor Kinase.- 3. Insulin Stimulates IGF-II Receptor Recycling.- 4. The Epidermal Growth Factor Receptor as a Target for Phorbol Diester Action.- 5. Conclusions.- References.
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