Description
Humana Press Inc. Molecular Cloning of Hormone Genes by Joel F. Habener
The peptide hormones are small proteins that regulate cellular metabolism through their specific interactions with tissues of the endocrine, nervous, and immune systems, as well as in embry onic development. During the past ten years, refinements in the techniques of recombinant DNA technology have resulted in the cloning of genes encoding approximately 50 different hormonal and regulatory peptides, including those in which the peptides themselves and the mRNAs encoding the peptides are present in only trace amounts in the tissues of origin. In addition to provid ing the coding sequences of recognized hormonal and regulatory peptides, gene sequencing has uncovered new bioactive peptides encoded in the precursor pro hormones that are then liberated along with the hormonal peptides during cellular cleavages of the precursors. The encoding of multiple peptides in a single mono cistronic mRNA appears to be a genetic mechanism for the gener ation of biologic diversification without requiring amplification of gene sequences. Two of the objectives in the assembly of this book are to pre sent, in one volume, the known primary structures of the genes encoding several of the polypeptide hormones and related regulatory peptides, and to provide an account of the various ap proaches that have been used to identify and select the cloned genes encoding these polypeptides. The contents of the two in troductory chapters are intended to provide the reader with a brief background of the approaches to gene cloning and the struc ture and expression of hormone-encoding genes._x000D_ Table of contents :- _x000D_
1 Approaches to Gene Cloning.- 1. Introduction.- 2. Construction and Analysis of Recombinant DNA.- 3. Techniques of Identification.- 4. Cloning Techniques.- 5. Hybridization Probes.- References.- 2 Gene Structure and Regulation.- 1. Introduction and Background.- 1.1. Discovery of Endocrine and Neurocrine Secretions.- 1.2. Investigations of Early Evolutionary Origins of Peptides as Hormones and Local Regulatory Peptides.- 1.3. Present Information Based on Molecular and Cellular Biology.- 2. The Structure and Organization of Genes.- 3. Precursors of the Peptide Hormones.- 3.1. Precursor Sequences Signal Intracellular Segregation.- 3.2. Many Peptide Hormone Precursors Are Polyproteins That Encode Multiple Peptides.- 3.3. Coding Sequences of Genes Are Interrupted.- 4. The Generation of Biologic Diversity.- 5. Gene Expression.- 5.1. Regulation of Gene Expression.- 5.2. cis and trans Mechanisms of Gene Regulation.- 6. Tissue-Specific Gene Expression.- 7. Coupling of Effector Action to Cellular Response.- References.- 3 Insulin Genes: Molecular Cloning and Analyses.- 1. Introduction.- 2. Molecular Cloning Strategies.- 3. Structure and Expression of the Insulin Gene.- 4. Polymorphism in the Human Insulin Genes.- 5. Abnormal Human Insulins.- References.- 4 The Glucagon Genes.- 1. Introduction.- 1.1. Background.- 1.2. Recombinant cDNAs Encoding Preproglucagon.- 2. Cloning and Characterization of Rat Preproglucagon mRNAs and cDNAs.- 2.1. Preproglucagon cDNAs.- 2.2. Hybridization Analysis of Preproglucagon mRNA.- 3. Glucagon Gene Cloning and Structural Analysis.- 3.1. Hybridization Analysis of the Glucagon Chromosomal Gene.- 3.2. Structural Analyses of the Rat Glucagon Gene.- 3.3. Experimental Procedures Used for the Isolation of a Recombinant Bacteriophage Containing the Rat Glucagon Gene.- 3.4. Partial Nucleotide Sequence Analysis of Gene Subclones.- 3.5. Promoter and Transcriptional Initiation Sites of the Rat Glucagon Gene.- 4. Implications Derived From the Structure of the Glucagon Gene.- 4.1. Evolution of the Glucagon Gene.- 4.2 Tissue-Specific Processing of Preproglucagon.- References.- 5 The Somatostatin Genes.- 1. Introduction.- 2. Anglerfish Somatostatins.- 3. Mammalian Somatostatin.- 4. Future Directions.- References.- 6 The Human Growth-Hormone Gene Family.- 1. Introduction.- 2. Map of the GH Locus.- 3. Sequences of the GH Family Members.- References.- 7 Glycoprotein Hormone Genes.- 1. Introduction.- 1.1. General Considerations.- 1.2. Structure of Glycoprotein Hormones.- 1.3. Major Questions.- 2. Molecular Cloning of Genes Encoding the Subunits of Glycoprotein Hormones.- 2.1. Molecular Cloning of ?-Subunit cDNAs.- 2.2. Molecular Cloning of the Genes Encoding the ?-Subunit of Glycoprotein Hormones.- 2.3 Molecular Cloning of cDNA Encoding the ?-Subunit of Human CG.- 2.4. Molecular Cloning of the Genes Encoding the Human CG?-LH? Subunits.- 2.5. Molecular Cloning of cDNA Encoding the Rat LH?-Subunit.- 2.6. Molecular Cloning of the Gene Encoding the Rat LH?-Subunit.- 2.7. Molecular Cloning of cDNA Encoding the TSH?-Subunit.- 2.8. Molecular Cloning of the Genes Encoding the TSH?- and FSH? Subunits.- 2.9. Chromosomal Localization of the Subunit Genes of Glycoprotein Hormones.- 3. Expression of the Subunit Genes.- 4. Summary.- References.- 8 Oxytocin and Vasopressin Genes: Expression and Structure.- 1. Introduction.- 2. Elucidation of the Precursor Structures.- 2.1. Cloning Strategy.- 2.2. Structure-Function Relations.- 3. Maturation of the Precursors.- 4. Vasopressin and Oxytocin Genes.- 4.1. Implications of the Gene Structures.- 4.2. Transcriptional Control.- 5. The Vasopressin Gene in Diabetes Insipidus (Brattleboro) Rats.- 5.1. Gene Sequence and the Predicted Vasopressin Precursor.- 5.2. Transcription and Translation.- 6. Expression of the Oxytocin Gene in Peripheral Organs.- 7. Polyprotein Structures and Their Implications.- References.- 9 The Proopiomelanocortin Genes.- 1. Introduction.- 2. Cloning of POMC Complementary DNA.- 3. POMC Gene Structure.- 4. Applications of Recombinant-DNA Probes to the Study of POMC Gene Expression.- 5. Summary.- References.- 10 Enkephalin Genes.- 1. Introduction.- 1.1. Nature of the Peptides.- 1.2. Physiologic Importance.- 1.3. Rationale for Analyzing the Genes.- 1.4. Screening Approaches.- 2. mRNA Characterization and Gene Structure.- 2.1. Characterization of Proenkephalin and Prodynorphin mRNAs.- 2.2. Molecular Cloning of Bovine and Human Proenkephalin mRNAs.- 2.3. Isolation of the Human Proenkephalin Gene.- 2.4. Isolation and Characterization of the Rat Proenkephalin mRNA and Gene.- 2.5. Isolation of the Toad Proenkephalin Gene.- 2.6. Molecular Cloning of Porcine and Human Prodynorphin mRNAs.- 2.7. Isolation of the Human Prodynorphin Gene.- 2.8. Isolation of the Rat Prodynorphin Gene.- 2.9. Summary of Structural and Evolutionary Considerations.- References.- 11 Calcitonin and Calcitonin-Related Peptide Genes: Tissue-Specific RNA Processing.- 1. Introduction.- 2. Calcitonin Gene Expression.- 2.1. Structure of the RNA Products of Calcitonin Gene Expression.- 2.2. Identification of a Second Mature Transcript of the Calcitonin Gene.- 2.3. Calcitonin Gene Expression in the Brain.- 2.4. Identification of a Second CGRP-Related mRNA.- 2.5. Similar RNA-Processing Events Operate in Human Calcitonin Gene Expression.- 3. Mechanisms of Tissue-Specific RNA-Processing Events.- 4. Conclusions.- References.- 12 Parathyroid Hormone Genes.- 1. Introduction.- 2. Isolation of PTH Genes.- 3. Gene Number, Location, and Polymorphisms.- 4. Structure of Mammalian PTH Genes.- 4.1. Introns.- 4.2. Promoter Sequences.- 4.3. Exons.- 5. Conclusion.- References.- 13 The Renin Gene.- 1. Introduction.- 2. The Renin-Angiotensin System-Its Importance in the Regulation of Blood Pressure.- 3. Renin: A Member of the Aspartyl Protease Family?.- 4. The Genetic System in the Mouse.- 5. Cloning of the Mouse Submaxillary Renin cDNA.- 5.1. Translation of Mouse Submaxillary Renin mRNA.- 5.2. Cloning of Mouse Submaxillary Renin cDNA and Genetic Differential Screening.- 5.3. cDNA Sequence.- 6. Structure and Processing of Mouse and Human Renin.- 6.1. Structure of Mouse Submaxillary Preprorenins-A Model for Renin Processing.- 6.2. Structure of Mouse Kidney Renin Deduced From Genomic Sequence.- 6.3. Structure of Human Kidney Renin Deduced From cDNA Sequence.- 7. Structure of the Renin Gene and Comparison With Other Aspartyl Proteases.- 8. Tissue-Specific Expression of the Renin Gene.- 9. Conclusion.- References.- 14 Nerve Growth Factor: mRNA and Genes That Encode the ?-Subunit.- 1. Introduction.- 2. Cloning of DNA Complementary to the mRNA That Encodes the ?-Subunit of Nerve Growth Factor.- 3. Human ?-NGF Gene.- 4. Structure of ?-NGF mRNA and Gene.- 5. Structure of the ?-NGF Precursor Encoded by ?-NGF mRNA and Gene.- 6. Knowledge Gained-and the Future.- References.- 15 Bombesin-Like Peptide Genes.- 1. Introduction.- 2. Structure of Bombesin-Like Peptides.- 2.1. Amphibian Bomebesin-Like Peptides.- 2.2. Mammalian Bombesin-like Peptides.- 2.3. Conclusions.- 3. Distribution and Physiology.- 3.1. Gastrin-Releasing Peptide.- 3.2. Mammalian Ranatensin.- 4. Molecular Biology.- 4.1. Gastrin-Releasing Peptide.- 4.2. Amphibian Bombesin-Like Peptides.- 5. Summary and Perspectives.- 6. Acknowledgments.- References.- 16 Biosynthesis of Peptides in the Skin of Xenopus laevis: cDNAs Encoding Precursors of Caerulein, PGLa, Xenopsin, and Thyrotropin-Releasing Hormone.- 1. Introduction.- 2. Precursor Sequences Deduced From Cloned cDNAs.- 2.1. Precursors of Caerulein.- 2.2. Precursor for PGLa, A New Peptide From the Skin of X. laevis.- 2.3. Precursor of Xenopsin.- 2.4. Precursor of Thyrotropin-Releasing Hormone.- 2.5. Comparison of the Precursors for Caerulein, PGLa, and Xenopsin.- 3. Conclusions.- References.- 17 cDNA Encoding Precursors of the Bee-Venom Peptides Melittin and Secapin.- 1. Introduction.- 2. Cloning and Sequence Analysis of Melittin mRNA.- 3. Sequence Analysis of the Cloned mRNA and Preprosecapin.- References.- 18 Yeast ?-Factor Genes.- 1. Introduction.- 2. Cloning of MF?l Using a Genetic Technique.- 3. Structure of MF?l.- 4. Cloning of MF?l and MF?2 by Hybridization.- 5. Structure of MF?2 and Comparison of MF?l and MF?2.- 6. Precursor Processing.- 7. Function of MF?1 vs MF?2.- 8. Summary.- References._x000D_
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