Peptide Growth Factors and Their Receptors II

Section B: Individual Growth Factors and Their Receptors (Cont’d from Part I).- 19 Interferons.- A. What Are Interferons?.- B. Structure of Interferon Genes and Proteins.- I. Interferon-?/? (Type I IFN).- 1. Human IFN-?/? Genes and Proteins.- 2. IFN-?/? Genes and Proteins of Other Animal Species.- II. Interferon-? (Type II IFN).- C. Interferon Induction and Production.- I. Production of IFN-?/?.- II. Molecular Mechanisms of IFN-?/? Induction.- III. IFN-? Induction.- D. Interferon Receptors.- I. IFN-?/? Receptor.- II. IFN-? Receptor.- E. Interferon Actions.- I. Molecular Mechanisms.- 1. Proteins Induced by the Interferons.- 2. Mechanisms of Gene Activation by Interferons.- 3. Common Mechanisms of Gene Activation by Interferons, Viruses, Double-Stranded RNA, Growth Factors, and Cytokines.- II. Spectrum of Biological Activities.- 1. Inhibition of Cell Growth.- 2. Stimulation of Cell Growth.- 3. Other Biological Activities.- 4. Possible Physiological Roles.- 5. Roles in Pathophysiology and Therapeutic Applications.- References.- 20 Cachectin/Tumor Necrosis Factor and Lymphotoxin.- A. Introduction.- B. “Factor-Mediated” Diseases: The Hematopoietic Origin of Factors.- C. Cachectin.- D. Tumor Necrosis Factor.- E. Physical Structure of Cachectin/TNF: Homology to Lymphotoxin.- F. Cachectin/TNF and Lymphotoxin: Production Sources, Kinetics, and Stimuli.- G. Control of Cachectin Gene Expression.- H. Cachectin/TNF Receptor and Postreceptor Mechanisms.- J. Biological Effects of Cachectin/TNF and Lymphotoxin: In Vivo and In Vitro.- I. Adipose Tissue.- II. Muscle.- III. Liver.- IV. Gastrointestinal Tract.- V. Central Nervous System.- VI. Adrenal.- VII. Skin.- VIII. Bone and Cartilage.- IX. Vascular Endothelium.- X. Hematopoietic Elements.- 1. Neutrophils.- 2. Eosinophils.- 3. Monocyte/Macrophages.- 4. Lymphocytes.- K. Gross Physiologic and Pathologic Consequences of Cachectin/TNF Production or Administration.- L. Disease States Associated with Elevated Levels of Cachectin/TNF.- M. Cachectin/TNF and Its Clinical Applications: To Be or Not To Be.- References.- 21 Bombesin and Gastrin-Releasing Peptide: Neuropeptides, Secretogogues, and Growth Factors.- A. Introduction.- B. Structure and Cellular Localization of the Peptides.- I. Bombesin-Related Peptides.- II. Structure of Bombesin and GRP.- III. Molecular Forms of GRP.- IV. Cellular Localization of GRP.- 1. Neuronal GRP.- 2. Neuroendocrine GRP.- C. Molecular Genetics of the Prepro-GRP Gene.- I. The Human Prepro-GRP Gene.- 1. Structure.- 2. Expression.- 3. Regulation.- II. Rat Prepro-GRP Gene.- 1. Structure.- 2. Expression.- III. Human Pro-GRP-Derived Peptides.- 1. Posttranslational Processing.- 2. Expression.- D. Pharmacological Effects of Bombesin and GRP.- I. Effects Unrelated to Growth.- 1. In Vivo Effects.- 2. In Vitro Effects on Isolated Organs.- 3. Direct Effects and Cellular Distribution of Receptors.- 4. Induced Release of Endogenous GRP.- II. Effect on Growth.- 1. In Vitro Studies.- 2. In Vivo Studies.- E. Cellular Responses to Bombesin and GRP.- I. Introduction to Bombesin-Mediated Signal Transduction.- II. Bombesin Binding to Cells/Membranes: Definition of the Bombesin Receptor.- III. Desensitization/Internalization of the Receptor.- IV. Phospholipase Activation.- V. Guanine Nucleotide-Binding Protein/Bombesin Receptor Interaction.- VI. Ion Fluxes.- VII. Protein Phosphorylation.- VIII. Bombesin Receptor Antagonists.- IX. Consequences of Bombesin-Evoked Second Messenger Production.- 1. Secretion.- 2. Receptor Transmodulation.- 3. Protooncogene Expression.- 4. DNA Synthesis.- F. Conclusions.- References.- 22 Platelet-Derived Endothelial Cell Growth Factor.- A. Introduction.- B. Purification and Biochemical Characterization of PD-ECGF.- I. Purification of PD-ECGF.- II. Structural Properties of PD-ECGF.- C. Primary Sequence of PD-ECGF.- D. Biological Activities of PD-ECGF.- I. In Vitro Effects of PD-ECGF.- II. In Vivo Effects of PD-ECGF.- E. Conclusion.- References.- 23 Nerve Growth Factor.- A. Introduction.- B. Nerve Growth Factor Gene Structure.- I. Nerve Growth Factor Protein Complex.- II. Gene Structure.- III. Nerve Growth Factor Gene Promoter.- IV. Amino Acid Sequence.- V. Expression of Cloned NGF.- VI. The ?- and ?-Subunits.- C. In Vivo Expression of NGF.- D. Mechanism of Signal Transduction.- I. Second Messengers.- II. Role of Oncogenes.- III. Genes Induced by NGF.- 1. Early Response Genes.- 2. Later Responses.- E. Receptor for NGF.- I. Biochemical Analysis.- II. Cloning of the NGF Receptor Gene.- III. Features of the NGF Receptor Gene.- IV. Kinetic Forms of the NGF Receptor.- V. Expression of Cloned NGF Receptors.- F. Conclusions.- References.- 24 A Glia-Derived Nexin Acting as a Neurite-Promoting Factor.- A. Introduction.- B. A Glia-Derived Neurite-Promoting Factor Acting as a Protease Inhibitor.- I. Biochemical Properties.- II. Molecular Cloning.- III. Characteristics of the Primary Structures.- IV. Biological Effects.- V. Localization of Glia-Derived Nexin.- VI. Glia-Derived Nexin, a Representative of a New Family of Neurite-Promoting Factors?.- VII. Mode of Action of GDN?.- VIII. In Vivo Relevance of the Balance Between Proteases and Protease Inhibitors for Neurite Outgrowth?.- C. Conclusion.- References.- 25 Mullerian Inhibiting Substance.- A. Introduction.- B. Structure of MIS.- I. Bovine and Chicken MIS Proteins.- II. Bovine and Human MIS Genes.- III. Biosynthesis of Human MIS in CHO Cells.- C. MIS as a Member of the TGF-? Family.- I. Structural Properties of the Family.- II. Proteolytic Processing of Human MIS.- D. MIS Expression During Development.- I. Upstream Regions of the Bovine and Human MIS Genes.- II. Expression of MIS in the Testis.- III. Expression of MIS in the Ovary.- E. Mechanism of Action.- I. MIS Receptor and Mullerian Duct Regression.- II. Modulators of MIS Action and Mullerian Duct Regression.- F. Potential Activities of MIS.- I. Descent of the Testis.- II. Fetal Lung Development.- III. Antiproliferative Effects of MIS.- G. Summary.- References.- 26 The Inhibin/Activin Family of Hormones and Growth Factors.- A. Chemical Characterization of Inhibins and Activins.- I. Inhibin.- II. Activin.- B. Actions of Inhibin and Activin on the Anterior Pituitary.- C. Development of Antisera Toward Inhibin Subunits.- D. Gonadal Production of Inhibin.- I. Granulosa Cells.- II. Sertoli Cells.- E. Intragonadal Actions of Inhibin and Activin.- I. Paracrine Regulation.- II. Autocrine Regulation.- F. Role of Inhibin in Regulation of FSH Secretion In Vivo.- I. Female Rat.- II. Male Rat.- G. Tissue Expression of Inhibin Subunits.- H. Inhibin and Activin in the Placenta.- I. Activin and the Control of Oxytocin Secretion.- J. Roles of Activin and Inhibin in Erythropoiesis.- I. Complexity of Hematopoietic Control.- II. Induction of Erythroid Differentiation.- III. Potentiation of Erythroid Colony Formation.- IV. Expression of Activin/Inhibin Subunits in Hematopoietic Cells.- K. Conclusions.- References.- 27 Mammary-Derived Growth Inhibitor.- A. Introduction.- B. Results.- I. Purification.- II. Amino Acid Sequence Determination and Sequence Homologies.- III. Cellular Activities.- 1. Ehrlich Ascites Carcinoma Cells.- 2. Mammary Epithelial Cell Lines.- IV. Biochemical and Cellular Mechanism of Action.- 1. Interaction with Hydrophobic Ligands.- 2. Possible Role of Ribonucleotide Reductase.- C. Conclusions.- References.- 28 Pentapeptide Growth Inhibitors.- A. Hemoregulatory Peptide.- I. Preparation of the Hemoregulatory Peptide.- 1. Sources.- 2. Fractionation.- II. Structural Studies.- III. Synthesis.- IV. Biological Activities on Normal Hematopoiesis.- 1. Growth-Promoting Activity of HP5b Dimer.- 2. Growth Inhibitory Activity of HP5b Monomer.- 3. Effects on Leukemic Cell Lines.- 4. Specificity Tests and Activities not Related to Growth.- V. Effects on Perturbed Hematopoiesis.- 1. Inhibitory Effects of HP5b Monomer.- 2. Possible Clinical Implications.- VI. Biochemical and Cellular Mechanisms of Action.- B. Epidermal Inhibitory Pentapeptide.- I. Purification Procedures.- II. Biological Properties.- III. Long-Term Effects.- IV. Repeated Treatments with the Epidermal Pentapeptide.- V. Tissue Specificity.- VI. Epidermal Regeneration and Malignancy.- VII. Species Specificity.- VIII. Toxicity.- IX. Precursors.- X. Possible Clinical Applications.- C. Conclusion.- References.- Section C: Coordinate Actions of Growth Factors in Specific Tissues or Cells.- 29 Coordinate Actions of Hematopoietic Growth Factors in Stimulation of Bone Marrow Function.- A. Introduction.- B. Stem Cells, Growth Factors, and the Extracellular Matrix.- C. Hematopoietic Growth Factor Interactions with Early Stem Cells.- I. Hematopoietic Growth Factor Interactions in the HPP-CFU Assay.- II. Action of IL-1 in Short-Term Marrow Suspension Culture (Delta Assay).- III. Hematopoietic Growth Factor Interactions in the Blast Cell Colony Assay.- IV. Inhibitory Influences on Hematopoietic Stem Cells and Progenitor Cells.- D. Synergistic Interactions Between IL-1, IL-3, and IL-5 in the Production and Activation of Eosinophils.- E. Hematopoietic Growth Factors and Basophil/Mast Cell Development.- F. Preclinical In Vivo Experience with Hematopoietic Growth Factors.- I. Murine Studies.- 1. In Vivo Interaction Between IL-1 and G-CSF in Mice Treated with 5-FU.- II. Primate Studies.- G. Clinical Experience with G- and GM-CSF.- I. CSFs in Chemotherapy-Induced Neutropenia.- II. CSFs in Autologous Bone Marrow Transplantation.- III. CSFs in Myelodysplastic Syndromes.- IV. In Vivo Studies of G-CSF in Congenital and Idiopathic Neutropenia.- H. Conclusions.- References.- 30 Peptide Growth Factors and the Nervous System.- A. Embryogenesis of Neural Tissues.- B. Progenitor Cells in the Neural Crest.- I. Melanocytes Are a Terminally Differentiated Cell Type.- II. Heterogeneity of Cell Types Within the Neural Crest.- III. SIF Cells Arise from HNK-1+ Progenitor Cells.- IV. SIF Cells Are Bipotential Progenitor Cells Within the Sympathoadrenal Lineage.- V. Does NGF Direct SIF Cells Toward Production of Sympathetic Neurons In Vivo?.- VI. Neurotransmitter Choice is Determined by Environmental Factors.- C. CNS Progenitor Cells Give Rise to Both Neurons and Glial Cells..- D. Identification of CNS Progenitor Cells In Vitro.- E. The 02A Glial Lineage.- I. PDGF is Mitogenic for 02A Progenitor Cells.- II. IGF-1 and CNTF Direct the 02A Lineage Toward Production of Oligodendrocytes or Type-2 Astrocytes.- F. Neural Growth Factors.- References.- 31 Role of Growth Factors in Cartilage and Bone Metabolism.- A. Origin of Growth Factors in Bone and Cartilage.- B. Receptors for Growth Factors in Bone and Cartilage.- C. Growth Factors in Bone Formation.- D. Growth Factors in Cartilage.- E. Growth Factors in Bone and Cartilage Induction.- F. Regulation of Growth Factor Activity in Bone and Cartilage.- G. Growth Factors and Cartilage Destruction.- H. Growth Factors and Disorders of Bone and Cartilage.- I. Potential for Growth Factors as Therapeutic Agents in Diseases of Bone Loss.- References.- 32 Role of Lymphokines in the Immune System.- A. Introduction.- I. Growth Regulation in the Immune System.- II. Organization of the Immune System.- III. T Lymphocytes.- 1. TH1 and TH2 Cells.- IV. B Cells.- V. Receptor-Mediated Signaling.- VI. Cognate T-Cell-B-Cell Interactions.- VII. Secreted T-Cell Regulatory Proteins (Lymphokines).- 1. Functions of Selected Lymphokines.- VIII. Lymphokines Produced by TH1 and TH2 Cells; Implications for Immune Functions.- B. Role of Lymphokines in the Immune Response.- I. T-Cell Subsets.- II. Functional Differences Between TH1 and TH2 Cells.- III. Surface Markers of the Different TH-Cell Subtypes.- IV. Proliferative Response of Clones of TH1 and TH2 Cells.- V. Regulation of the Activation of TH1 and TH2 Cells.- VI. TH1 and TH2 Cells In Vivo.- C. Action of Lymphokines on Macrophages.- D. Actions of Lymphokines in B-Cell Responses.- I. Activation.- II. Growth Stimulation.- III. Differentiation of B Cells into Antibody-Producing Cells.- IV. Lymphokine Regulation of Ig Class Switching.- V. B-Cell Growth and Development Control by Action of T-Cell-Derived Lymphokines.- E. Conclusions.- I. Lymphoid Organs.- II. Immune Responses Against Bacterial Antigens.- III. Immune Response to Viral Antigens.- IV. Immune Response to Parasites.- V. Concluding Remarks.- References.- 33 Coordinate Actions of Growth Factors in Monocytes/Macrophages.- A. Introduction.- B. Migration.- C. Extramedullar Proliferation.- D. Changes in Shape.- E. Endocytosis, Cell Surface Receptors, and Antigens.- I. Endocytic Receptors.- II. Other Surface Antigens.- F. Secretion.- I. Cytokines.- II. Complement Components and Other Proteases.- III. Sterols.- IV. Reactive Intermediates of Oxygen and of Nitrogen.- G. Activation.- I. Killing of Microbial Pathogens.- II. Killing of Host-Type Cells.- III. Promotion of Wound Healing.- IV. Generation of Inflammatory and Immune Responses.- V. Scavenging of Senescent Cells.- H. Deactivation.- I. Mechanisms of Action of Cytokines on Macrophages.- J. Autocrine Effects.- K. Polymorphonuclear Leukocytes..- L. Conclusions.- References.- 34 Extracellular Matrices, Cells, and Growth Factors.- A. Introduction.- B. Nature of Extracellular Matrices.- I. Collagens.- II. Glycoproteins.- III. Proteoglycans.- IV. Matrix Molecules in Supramolecular Complexes.- C. Cell-Matrix Interactions.- I. Fibronectin.- II. Laminin.- III. Collagen.- IV. Matrix Receptors.- D. Role of Matrix Molecules in Cell Growth.- I. Storage Sites for Growth Factors.- II. Mitogenic Activities of Fibronectin and Laminin.- III. Termination of Proliferation by Collagen.- E. Induction of Collagenase by Growth Factors — Role in Proliferation.- References.- Section D: Processes Regulated by Growth Factors.- 35 Induction of Proteases and Protease Inhibitors by Growth Factors.- A. Introduction.- B. Fibroblast Growth Factor.- C. Transforming Growth Factor-?.- D. Platelet-Derived Growth Factor.- E. Epidermal Growth Factor.- F. Interleukin-1.- I. Hemostasis.- II. Cancer.- III. Glomerulonephritis.- IV. Arthritis.- G. Tumor Necrosis Factor.- H. Colony-Stimulating Factor 1.- I. Discussion.- References.- 36 Inflammation and Repair.- A. Introduction.- B. Inflammatory Phase: Inflammatory Cell Recruitment and Function.- I. Platelets.- II. Neutrophils.- III. Monocytes/Macrophages.- IV. Lymphocyte Function and Regulation.- C. Proliferative Phase.- I. Regulation of Fibroblast Proliferation.- II. Extracellular Matrix Synthesis.- 1. Collagen.- 2. Proteoglycans.- 3. Fibronectin.- III. Endothelial Cell Function and Angiogenesis.- D. Remodeling Phase: Matrix Turnover and Fibrotic Disorders.- E. Concluding Remarks.- References.- 37 Angiogenesis.- A. Introduction.- B. Bioassays for Angiogenesis.- I. In Vivo Methods.- II. In Vitro Methods.- C. Angiogenic Factors.- I. Fibroblast Growth Factors.- II. Angiogenin.- III. Transforming Growth Factor-?.- IV. Transforming Growth Factor-?.- V. Tumor Necrosis Factor.- VI. Platelet-Derived Endothelial Cell Growth Factor.- VII. Angiotropin.- VIII. Low Molecular Weight Nonpeptide Angiogenesis Factors.- IX. Mechanisms of Angiogenesis Factor Action.- D. Physiological Regulation of Angiogenic Molecules.- I. Role of Extracellular Matrix in Modulating Angiogenic Factors.- II. Mast Cells and Heparin as Potentiators of Angiogenesis.- III. Storage of Basic FGF in Basement Membrane — Role of Heparan Sulfate.- IV. Regulation of Angiogenic Factors by Pericytes.- V. Endocrine Regulation of Angiogenesis.- 1. Ovary.- 2. Endometrium.- 3. Placenta.- VI. Role of Hypoxia in Regulating Angiogenic Factors.- E. Pathological Angiogenesis.- F. Angiogenesis Inhibitors.- G. Future Directions.- References.- 38 Metastasis.- A. Introduction.- B. Invasion as an Active Process.- C. Interaction of Tumor Cells with the Extracellular Matrix.- D. Three Stages in Invasion.- E. Agents Inducing Migration: Autocrine Motility Factors.- F. Melanoma Autocrine Motility Factor.- I. Isolation and Characterization.- II. Some Chemical Properties of the Protein.- III. Signal Transduction in Tumor Cells.- G. Unique Features of Tumor Cell Motility.- H. Growth Factors as Motility Stimulants.- I. Thrombospondin.- II. Bombesin.- III. Insulin-Like Growth Factors.- I. Autocrine Motility Responses in Nontransformed Cells.- J. Autocrine Motility Factors as Markers of Malignancy.- References.- 39 Expression of Growth Factors and Their Receptors in Development.- A. Introduction.- B. The EGF/TGF-?Family of Growth Factors.- I. Epidermal Growth Factor.- 1. Introduction.- 2. Developmental Expression of the EGF Receptor.- 3. Biological Actions of Exogenous EGF.- 4. Developmental Expression of EGF.- 5. Transplacental Transport of Maternal EGF.- II. Transforming Growth Factor-?.- 1. Introduction.- 2. Developmental Expression of TGF-?.- III. Link Between EGF-Related Growth Factors and Homeotic Loci.- IV. Developmental Expression of the Neu Oncogene.- C. ?-Type TGFs.- I. Introduction.- II. Developmental Expression ofTGF-?.- III. Role for TGF-? in Amphibian Development.- D. Insulin-Like Growth Factors/Somatomedins.- I. Introduction.- II. Expression of IGF Receptors and Binding Proteins.- III. IGFs in Fetal Tissues and Fluids.- IV. Developmental Expression of IGF Genes.- E. Platelet-Derived Growth Factor.- I. Introduction.- II. Developmental Expression of PDGF.- F. Fibroblast Growth Factor and Related Molecules.- I. Introduction.- II. Developmental Expression of FGF.- III. Developmental Expression of Related Molecules.- G. Hematopoietic Growth Factors.- I. Colony-Stimulating Factor 1 and Its Receptor (c-fms)..- 1. Introduction.- 2. Developmental Expression of c-fms.- II. Related Growth Factors.- III. Interleukins-2 and -4.- H. Nerve Growth Factor.- I. Introduction.- II. Localization of NGF and Its Receptor.- I. Conclusions.- References.- 40 Relationships Between Oncogenes and Growth Control.- A. Introduction.- B. Growth Factor Genes.- I. Growth Factor-Type Oncogenes.- 1. The v-sis Oncogene.- 2. The int-1 and int-2 Oncogenes.- 3. The hst Oncogene.- II. Growth Factor Genes Experimentally Shown to be Capable of Acting as Oncogenes.- C. Signal Transducer Genes.- I. Receptor Tyrosine Kinase-Type Oncogenes.- 1. The v-erbB Oncogene.- 2. The v-fms Oncogene.- 3. Other Receptor-Type Tyrosine Kinase Oncogenes.- II. Tyrosine Kinase-Type Oncogenes Lacking a Transmembrane Domain.- III. The ras Family Oncogenes.- IV. Serine Threonine Kinase-Type Oncogenes.- D. Genes Encoding Nuclear Proteins.- I. Immediate Early Genes.- 1. The fos Gene Family.- 2. The jun Gene Family.- II. Early Genes.- 1. The myc Gene Family.- III. Hormone Receptor Genes.- 1. The erbA Gene Family.- IV. Other Nuclear Oncogenes.- 1. The myb Gene Family.- 2. The ets Gene Family.- 3. The p53 Oncogene.- E. Cooperation Between Oncogenes.- References.- Appendix A. Alternate Names for Growth Factors.- Appendix B. Chromosomal Locations of Growth Factors/Growth Factor Receptors.