Peptide Growth Factors and Their Receptors I

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 entire 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 impossible for anyone person to stay informed on this subject by reading the primary literature. At the same time it is becoming increasingly apparent that 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 com­ mon language for intercellular communication. As a set they affect essentially 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. This treatise is divided into four main sections. After three introductory chapters, its principal focus is the detailed description of each of the major peptide growth factors in 26 individual chapters.

Contenu

Section A: Introduction.- 1 The Multifunctional Nature of Peptide Growth Factors.- A. Introduction.- B. Autocrine, Paracrine, and Endocrine Mechanisms of Action.- C. Range of Target Cells for Peptide Growth Factors.- D. Contextuality of Action.- E. Nuclear Transcription Factors are also Multifunctional.- F. Role of Extracellular Matrix in Mediating Interactions Between Cells.- G. Therapeutic Implications.- References.- 2 Isolation and Characterization of Growth Factors.- A. Introduction.- B. Insulin.- C. Nerve Growth Factor.- D. Epidermal Growth Factor.- E. Insulin-Like Growth Factors.- F. Platelet-Derived Growth Factor.- G. Fibroblast Growth Factors.- H. Transforming Growth Factors.- I. TGF-?.- II. TGF-?.- I. Interleukins.- J. Hemopoietic Growth Factors.- K. Concluding Remarks.- References.- 3 Properties and Regulation of Receptors for Growth Factors.- A. Introduction.- B. Extracellular Domain Structures of Growth Factor Receptors.- C. Ligand Binding Regions of Extracellular Domains.- D. Extracellular Receptor Domains as Serum Receptors.- E. Multiple Ligand Binding Capabilities of Growth Factor Receptors.- F. Regulation of Cell Surface Ligand Binding.- G. Transmembrane Domains.- H. Cytoplasmic Tyrosine Kinase Domain Structures.- I. Regulation of Receptor Tyrosine Kinases.- J. Cytoplasmic Domains Lacking Tyrosine Kinase Sequences.- K. Conclusions.- References.- Section B: Individual Growth Factors and Their Receptors.- 4 The Epidermal Growth Factor Family.- A. Introduction.- B. Structural Properties of the Growth Factors.- I. Amino Acid Sequences.- II. Related Sequences.- III. Physical Properties.- IV. High Resolution Structure.- 1. Polypeptide Backbone.- 2. Aromatic Clusters.- 3. TGF-? and EGF Comparisons.- 4. Hybrid Molecules.- V. Structure-Function Relationships.- 1. Site-Directed Mutagenesis.- 2. Growth Factor Fragments.- C. Precursor Molecules.- I. EGF.- II. TGF-?.- III. Pox Virus Growth Factors.- D. Growth Factor Genes.- I. Chromosomal Localization.- II. Gene Organization.- 1. Human EGF.- 2. Human TGF-?.- III. Gene Expression.- 1. EGF.- 2. TGF-?.- 3. Pox Virus Growth Factors.- E. The EGF Receptor.- I. Receptor Structure.- II. Receptor Gene.- 1. Chromosomal Localization.- 2. Gene Organization.- 3. Gene Expression.- III. Receptor Life Cycle.- 1. Biosynthesis.- 2. Endocytosis and Degradation.- IV. Receptor Function.- 1. Heterologous Receptor Expression.- 2. Mutants.- 3. Receptor Activation.- 4. Receptor Substrates.- 5. Activation of Gene Expression.- F. Physiology of the EGF Family.- I. EGF.- 1. Distribution in Fluids/Secretions.- 2. Biological Responses.- II. TGF-?.- III. Amphiregulin.- IV. Pox Virus Growth Factors.- G. Role in Transformation.- I. Growth Factor Studies.- 1. Correlative Information.- 2. Transfection Studies.- II. Receptor Studies.- 1. Correlative Information.- 2. Transfection Studies.- References.- 5 Platelet-Derived Growth Factor.- A. Introduction.- B. PDGF Molecules.- I. Multiple Forms and Amino Acid Sequence.- 1. Two Distinct but Homologous Chains Comprise PDGF.- 2. Structural Heterogeneity of PDGF.- 3. Structural Features of the PDGF Molecules.- 4. Structural Conservation of the PDGF Molecule.- II. Gene Structure of the A and B Chains of PDGF.- 1. Characteristics of the A-Chain Gene.- 2. Characteristics of the B-Chain Gene.- 3. Comparison of the A- and B-Chain Genes.- III. Expression and Secretion of PDGF by Normal Cells.- 1. PDGF is Expressed at Low or Undetectable Levels in Normal Cells.- 2. Inducible Expression and Secretion of PDGF.- IV. Expression and Secretion of PDGF in Transformed Cells.- V. Processing and Cellular Localization of PDGF Isoforms.- 1. Simian Sarcoma Virus-Transformed Cells.- 2. c-sis-Transformed Cells.- 3. PDGF A-Chain Transfectants.- 4. Cells Expressing Recombinant PDGF-AB Heterodimers.- 5. Transformed Cells.- 6. Normal Cells.- C. PDGF Receptors.- I. General Models of Receptor Structure and Properties.- 1. Old and New Models of the Structure of the PDGF Receptor.- II. Binding Properties of the PDGF Receptor.- 1. Practical or Technical Concerns.- 2. Receptor Specificity.- 3. Receptor Affinity and Number.- III. Cloning and Expression of Receptor cDNAs.- 1. The Receptor ?-Subunit cDNA.- 2. The Receptor ?-Subunit cDNA.- IV. The Receptor Subunit Genes.- V. Physical Characteristics of PDGF Receptor Proteins.- 1. Size of the PDGF Receptor Based on Affinity Crosslinking Studies.- 2. Size of the Mature Receptor Subunits Based on Metabolic Labeling Data.- 3. Isoelectric Point of Receptor Subunits.- VI. Biosynthesis and Turnover of Receptor Subunits.- 1. Predictions about ?-Subunit Biosynthesis Based on cDNA Sequence.- 2. Experimentally Determined Rates of Biosynthesis and Turnover of the ?-Subunit.- 3. Biosynthesis of the ?-Subunit.- VII. Purification of Receptor Proteins.- VIII. Activities of PDGF Receptors.- 1. Ligand-Induced Internalization.- 2. Ligand-Induced Receptor Autophosphorylation.- IX. Pattern of Expression of PDGF Receptors.- 1. Numbers of Receptors on Different Cell Types.- 2. Relative Levels of Expression of the Two Receptor Subunits in Different Cell Types.- X. Regulation of Expression or Properties of PDGF Receptors.- 1. Regulation of the Affinity of the PDGF Receptor.- 2. Acute Regulation of PDGF Receptor Expression.- 3. Regulation of PDGF Receptor Expression in Potential PDGF Autocrine Systems.- 4. Regulation of PDGF Receptor Expression During Embryogenesis, Development, and Wound Healing.- 5. Receptor Expression In Vivo.- D. In Vivo Clearance of PDGF and PDGF-Binding Proteins.- I. Rapid In Vivo Clearance of PDGF-AB.- II. PDGF-Binding Proteins.- E. Biochemical and Cellular Mechanism of Action.- I. Coordinate Control of Cell Proliferation by PDGF and Plasma Components.- II. Phospholipase Activation and Prostaglandin Metabolism.- III. Modulation of Ion Flux.- IV. Tyrosine Phosphorylation.- V. PDGF Induction of "Early Genes".- F. Biological Activity of PDGF in Vitro and In Vivo.- I. Direct and Indirect Effects of PDGF on Cell Growth In Vitro.- 1. Direct Mitogenic Response to PDGF.- 2. Indirect Effects of PDGF on Cell Growth.- II. Other In Vitro Activities of PDGF.- 1. Directed Cell Migration and Cell Activation in Response to PDGF.- 2. Modification of Cellular Matrix Constituents.- 3. Vasoconstriction.- III. PDGF In Vivo and Clinical Applications.- 1. Wound Repair.- 2. Embryogenesis and Development.- 3. Atherosclerosis.- 4. Neoplasia and Transformed Cells.- 5. Inflammatory Joint Disease.- 6. Fibrosis.- 7. Other Possible Disease Associations References.- Referen…