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HARDBACK price:$64.00 add to cart Rights & Permissions Free PDF Access Sign in to download PDF book and chapters Free Resources PDF SUMMARY Display this book on your site! Related Titles Applications of Toxicogenomic Technologies to Predictive Toxicology and Risk Assessment Toxicity Testing in the 21st Century: A Vision and a Strategy Other Related Titles Scientific Frontiers in Developmental Toxicology and Risk Assessment (2000) Commission on Life Sciences (CLS) Citation Manager Export the bibliographic data for this book in your chosen format Web Search Builder Use this book's key terms to search within this book, across our collection, or across the Web. Skim This Chapter Skim this chapter and use this chapter's key terms to search within this book. Reference Finder Paste in your own text to find books that relate to your topic. Citation Manager . "Appendix C Signaling Pathways." Scientific Frontiers in Developmental Toxicology and Risk Assessment. Washington, DC: The National Academies Press, 2000. Please select a format: Page 296   E-mail Share on facebook Facebook Share on delicious Delicious Share on stumbleupon Stumble Share on twitter Twitter More Sharing ServicesMore The following HTML text is provided to enhance online readability. Many aspects of typography translate only awkwardly to HTML. Please use the page image as the authoritative form to ensure accuracy. Appendix C Signaling Pathways Seventeen intercellular signal transduction pathways are currently known with regard to the identity of their ligands, transduction intermediates, kinases, and targets. These are illustrated in Panels 1-17. Several were discovered in the course of the analysis of developmental mutants of Drosophila. Since no new mutant has been discovered recently in the continuing analysis of mutants, it is expected that most are already known. Pathways 1-6 are used extensively in early development, for example, axis specification and germ layer formation, as well as later. Pathways 7-10 are used in later development, including organogenesis and tissue renewal. Pathways 11-17 are used extensively in the physiological function of differentiated cells of the fetus, juvenile, and adult. Approximately twelve intracellular pathways of checkpoint controls and molecular stress responses are currently known. Three are illustrated in Panels 18 and 19, and several are listed in Table 6-7. Panel 18 shows the ER-Golgi unfolded protein response, a molecular stress response of the cell to various chemical (e.g., ethanol, dithiothreitol) or physical (e.g. heat) conditions that lead to loss of function by protein unfolding (“denaturation”). The response leads to increased chaperone protein levels in the ER and Golgi, which increase refolding and restore function. The pathway also acts as a G1/S checkpoint control when naturally unstable proteins are produced. Panel 19 shows the p53 related stress response to DNA damage (genotoxic stress) leading to G1/S or G2/M arrest until repair is completed (upper half of panel). The pathway also acts as a checkpoint control monitoring DNA synthesis, imposing G2/M arrest until it is finished, via phosphorylation of the cdc25 phosphatase (lower half of panel). Page 296 Front Matter (R1-R20) Executive Summary (1-9) 1 Introduction (10-16) 2 Developmental Defects and Their Causes (17-25) 3 Current Practices for Assessing Risk for Developmental Defects and Their Limitations (26-57) 4 Mechanisms of Developmental Toxicity (58-87) 5 Human Genetics and the Human Genome Project (88-107) 6 Recent Advances in Developmental Biology (108-150) 7 Using Model Animals to Assess and Understand Developmental Toxicity (151-195) 8 A Multilevel Approach to Improving Risk Assessment for Developmental Toxicity (196-219) 9 Conclusions and Recommendations (220-244) References (245-278) Appendix A Glossary (279-289) Appendix B Database Descriptions (290-295) Appendix C Signaling Pathways (296-308) Appendix D Biographical Information on the Committee on Developmental Toxicology (309-312) Index (313-327)

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Scientific Frontiers in Developmental Toxicology and Risk Assessment Appendix C Signaling Pathways Seventeen intercellular signal transduction pathways are currently known with regard to the identity of their ligands, transduction intermediates, kinases, and targets. These are illustrated in Panels 1-17. Several were discovered in the course of the analysis of developmental mutants of Drosophila. Since no new mutant has been discovered recently in the continuing analysis of mutants, it is expected that most are already known. Pathways 1-6 are used extensively in early development, for example, axis specification and germ layer formation, as well as later. Pathways 7-10 are used in later development, including organogenesis and tissue renewal. Pathways 11-17 are used extensively in the physiological function of differentiated cells of the fetus, juvenile, and adult. Approximately twelve intracellular pathways of checkpoint controls and molecular stress responses are currently known. Three are illustrated in Panels 18 and 19, and several are listed in Table 6-7. Panel 18 shows the ER-Golgi unfolded protein response, a molecular stress response of the cell to various chemical (e.g., ethanol, dithiothreitol) or physical (e.g. heat) conditions that lead to loss of function by protein unfolding (“denaturation”). The response leads to increased chaperone protein levels in the ER and Golgi, which increase refolding and restore function. The pathway also acts as a G1/S checkpoint control when naturally unstable proteins are produced. Panel 19 shows the p53 related stress response to DNA damage (genotoxic stress) leading to G1/S or G2/M arrest until repair is completed (upper half of panel). The pathway also acts as a checkpoint control monitoring DNA synthesis, imposing G2/M arrest until it is finished, via phosphorylation of the cdc25 phosphatase (lower half of panel).

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Scientific Frontiers in Developmental Toxicology and Risk Assessment 1A. Wnt pathway via β–catenin 1B. Wnt pathway via JNK (planar cell polarity pathway)

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Scientific Frontiers in Developmental Toxicology and Risk Assessment 2. Receptor serine/threonine kinase (TGF-β receptor) pathway 3. Hedgehog pathway (Patched receptor protein)

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Scientific Frontiers in Developmental Toxicology and Risk Assessment 4. Receptor tyrosine kinase pathway (small G-protein [Ras] linked)

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Scientific Frontiers in Developmental Toxicology and Risk Assessment 5. Notch-Delta pathway 6. Receptor-linked cytoplasmic tyrosine kinase (cytokine) pathway

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Scientific Frontiers in Developmental Toxicology and Risk Assessment 7. IL1froll receptor; NF-kappaB pathway 8. Nuclear hormone receptor pathway

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Scientific Frontiers in Developmental Toxicology and Risk Assessment 9. Apoptosis pathway (cell death pathway)

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Scientific Frontiers in Developmental Toxicology and Risk Assessment 10. Receptor protein tyrosine phosphatase (RPTPs) pathway 11. Receptor guanylate cyclase pathway

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Scientific Frontiers in Developmental Toxicology and Risk Assessment 12. Nitric oxide receptor pathway 13. G-protein coupled receptor (large G-protein) pathway

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Scientific Frontiers in Developmental Toxicology and Risk Assessment 14. Integrin pathway 15. Cadherin pathway

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Scientific Frontiers in Developmental Toxicology and Risk Assessment 16. Gap junction pathway 17. Ligand-gated cation channel pathway

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Scientific Frontiers in Developmental Toxicology and Risk Assessment 18. A stress response: The unfolded protein response (UPR)

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Scientific Frontiers in Developmental Toxicology and Risk Assessment 19. Stress responses and checkpoints for DNA damage and replication.

Representative terms from entire chapter:

molecular stress