Peptide Growth Factors and Their Receptors I
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Peptide Growth Factors and Their Receptors I

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Michael B. Sporn
1199 g
236x154x48 mm
95 / 1, Handbook of Experimental Pharmacology

With contributions by numerous experts
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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 Pr
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.