Main description:

This two-volume treatise, the collected effort of more than 50 authors, represents the first comprehensive survey of the chemistry and biology of the set of molecules known as peptide growth factors. Although there have been many symposia on this topic, and numerous publications of reviews dealing with selected subsets of growth factors, the entired field has never been covered in a single treatise. It is essential to do this at the present time, as the number of journal articles on peptide growth factors now makes it almost im anyone person to stay informed on this subject by reading the possible for At the same time it is becoming increasingly apparent that primary literature. these substances are of universal importance in biology and medicine and that the original classification of these molecules, based on the laboratory setting of their discovery, as "growth factors," "lymphokines," "cytokines," or "colony-stimulating factors," was quite artifactual; they are in fact the basis of a common language for intercellular communication. As a set they affect es sentially every cell in the body, and in this regard they provide the basis to develop a unified science of cell biology, germane to all of biomedical research.

Contents:

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.