Mechanisms of Receptor Regulation

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.