Summary
Leading scientists summarize the latest findings on signal transduction and cell cycle regulation and describe the effort to design and synthesize inhibiting molecules, as well as to evaluate their biochemical and biological activities. They review the relevant cell surface receptors, their ligands, and their downstream pathways. Also examined are the latest findings on the components of novel signaling networks controlling the activity of nuclear transcription factors and cell cycle regulatory molecules. Cutting-edge and highly suggestive, Signaling Networks and Cell Cycle Control: The Molecular Basis of Cancer and Other Diseases presents a wealth of information on the emerging principles of the field, as well as an invaluable guide for all experimental and clinical investigators of cell regulation and its rapidly emerging pharmacological opportunities today.
Author Biography
Stuart A. Aaronson, MD: Derald H. Ruttenberg Cancer Center, Mount Sinai School of Medicine, New York Robert T. Abraham: Division of Oncology Research, Mayo Clinic and Foundation, Rochester, MN Peter Acs, MD: Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, MD Grant D. Barish, BS: Varmus Laboratory, National Cancer Institute, National Institutes of Health, Bethesda, MD Dipak K. Bhattacharyya, PHD: Laboratory of Cellular Carcinogensis and Tumor Promotion, National Cancer Institute, Bethesda, MD Peter M. Blumberg, PHD: Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, MD Lewis C. Cantley, PHD: Division of Signal Transduction, Beth Israel Deaconess Medical Center, Harvard Institutes of Medicine, Boston, MA Esther H. Chang, PHD: Department of Otolaryngology, Lombardi Cancer Center, Georgetown University Medical Center, Washington, DC Mario Chiarello, MD: Oral and Pharangeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD Yanfang Chu: Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD Geoffrey J. Clark, PHD: Department of Pharmacology, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, NC Adrienne D. Cox, PHD: Departments of Radiation Oncology and Pharmacology, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, NC Erik H. J. Danen, PHD: Craniofacial Developmental Biology and Regeneration Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD Roger J. Davis, PHD: Howard Hughes Medical Institute and Program in Molecular Medicine, Department of Biochemistry and Molecular Biology, University of Massachusetts Medical School, Worcester, MA Mark P. de Caestecker, MD, PHD: Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, Bethesda, MD Channing J. Der, PHD: Department of Pharmacology, Curriculum in Genetics and Molecular Biology, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, NC David T. Dudley, PHD: Department of Cell Biology, Parke-Davis Pharmaceutical Research, Ann Arbor, MI Erastus C. Dudley: Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD Gary R. Fanger: Program in Molecular Signal Transduction, Division of Basic Sciences, National Jewish Medical and Research Center, Denver, CO Paolo Fedi, MD, PHD: Derald H. Ruttenberg Cancer Center, Mount Sinai School of Medicine, New York, NY Toren Finkel, MD, PHD: Cardiology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD David A. Fruman, PHD: Division of Signal Transduction, Beth Israel Deaconess Medical Center, Harvard Institutes of Medicine, Boston, MA Shigetomo Fukuhara, PHD: Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD J. Silvio Gutkind, PHD: Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD Felicita Hornung: Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD Gary L. Johnson: Program in Molecular Signal Transduction, Division of Basic Sciences, National Jewish Medical and Research Center, Denver, CO Andrew Keightley, PHD: Department of Immunology, Cleveland Clinic Research Foundation, Cleveland, OH Kathleen Kelly: Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD David H. Kirn, MD: Vice President of Clinical Research, Onyx Pharmaceuticals, Richmond, CA, and Department of Medicine, University of California, San Francisco, CA Andrew C. Larner, MD, PHD: Department of Immunology, Cleveland Clinic Research Foundation, Cleveland, OH Robert J. Lechleider, MD: Department of Pharmacology, Uniformed University of the Health Sciences, Bethesda, MD Michael J. Lenardo: Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD Alexander Levitzki: Department of Biological Chemistry, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Israel Patricia S. Lorenzo, PHD: Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, MD Anthony M. Manning, PHD: Signal Pharmaceuticals, Inc., San Diego, CA Maria Julia Marinissen, PHD: Oral and Pharangeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD David A. Martin: Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD Bruce J. Mayer, PHD: Howard Hughes Medical Institute, Children's Hospital and Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, MA Frank Mercurio, PHD: Signal Pharmaceuticals, Inc., San Diego, CA Sheldon Milstien, PHD: Laboratory of Cellular and Molecular Regulation, National Institute of Mental Health, National Institutes of Health, Bethesda, MD John P. O'Bryan, PHD: Department of Pharmacology, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, NC Michele Pagano, MD: Department of Pathology and Kaplan Cancer Center, New York University Medical Center, New York, NY Kathleen F. Pirollo, PHD: Department of Otolaryngology, Lombardi Cancer Center, Georgetown University Medical Center, Washington, DC Katya Ravid, PHD: Department of Biochemistry and Witaker Cardiovascular Institute, Boston University School of Medicine, Boston, MA Anita B. Roberts, PHD: Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, Bethesda, MD Kevin M. Ryan, PHD: ABL-Basic Research Program, Frederick Cancer Research and Development Center, National Cancer Institute, Frederick, MD Alan R. Saltiel, PHD: Department of Cell Biology, Parke-Davis Pharmaceutical Research, Ann Arbor, MI Lawrence E. Samelson, MD: Laboratory of Cellular and Molecular Biology, National Cancer Institute, Bethesda, MD Edward A. Sausville, MD, PHD: Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD Thomas K. Schlesinger: Program in Molecular Signal Transduction, Division of Basic Sciences, National Jewish Medical and Research Center, Denver, CO Pamela L. Schwartzberg, MD, PHD: Laboratory of Genetic Disease Research, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD Adrian M. Senderowicz, MD: Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD Richard M. Siegel: Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD Reuben P. Siraganian, MD, PHD: Receptors and Signal Transduction Section, OIIB, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD Joanne Sloan-Lancaster, PHD: Research Technologies and Proteins, Eli Lilly and Company, Indianapolis, IN Sarah Spiegel, PHD: Department of Biochemistry and Molecular Biology, Georgetown University Medical Center, Washington, DC Daniel M. Sullivan, PHD: Cardiology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethsda, MD Marc Symons, PHD: The Picower Institute for Molecular Medicine, Manhasset, NY Randal S. Tibbets: Division of Oncology Research, Mayo Clinic and Foundation, Rochester, MN Karen H. Vousden, PHD: ABL-Basic Research Program, Frederick Cancer and Development Center, National Cancer Institute, Frederick, MD Jean Y. J. Wang, PHD: Department of Biology, Center for Molecular Genetics and the Cancer Center, University of California San Diego, La Jolla, CA Bart O. Williams, PHD: Varmus Laboratory, National Cancer Institute, National Institutes of Health, Bethesda, MD Liang Xu, MD, PHD: Department of Otolaryngology, Lombardi Cancer Center, Georgetown University Medical Center, Washington, DC Kenneth M. Yamada, MD, PHD: Craniofacial Developmental Biology and Regeneration Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD Peter R. Young: Department of Molecular Biology, SmithKline Beecham Pharmaceuticals, King of Prussia, PA Lixin Zheng: Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD
Table of Contents
| Preface |
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v | |
| Contributors |
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xi | |
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1 | (26) |
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Signal Transduction Through Tyrosine Kinase Growth Factor Receptors |
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27 | (12) |
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Signaling from TGF-β Receptors |
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39 | (14) |
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The Wnt Signal Transduction Pathway |
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53 | (30) |
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Signaling from G-Protein-Coupled Receptors to the Nucleus |
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83 | (16) |
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Proximal Events in T-Cell Activation |
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99 | (14) |
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Signal Transduction from the High Affinity IgE Receptor |
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113 | (22) |
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Signaling Through Fas (CD95, APO-1) and Related Death Receptors |
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135 | (18) |
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Signal Transduction to the Nucleus by MAP Kinase |
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153 | (12) |
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The Regulation of MAP Kinase Pathways by MAP Kinase Phosphatases |
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165 | (18) |
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Control of MAPK Signaling by Ste20- and Ste11-Like Kinases |
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183 | (30) |
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Ras Signaling and Transformation |
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213 | (18) |
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Signaling Pathways Controlled by Rho Family GTP-Binding Proteins |
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231 | (16) |
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P13-Kinases: Role in Signal Transduction |
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247 | (20) |
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P13K-Related Kinases: Roles in Cell-Cycle Regulation and DNA Damage Responses |
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267 | (36) |
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Integrative Signaling Through c-Ab1: A Tyrosine Kinase with Nuclear and Cytoplasmic Functions |
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303 | (22) |
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Src: A Model for Regulation of Intracellular Signaling Molecules |
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325 | (22) |
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Inhibitors of Protein Kinase C and Related Receptors for the Lipophilic Second Messenger sn-1,2-Diacylglycerol |
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347 | (18) |
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Reactive Oxygen Species in Proliferative Signaling |
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365 | (14) |
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Sphingolipid Metabolites in Signal Transduction |
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379 | (14) |
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The Jak/Stat Signaling Cascade: Its Role in the Biological Effects of Interferons |
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393 | (18) |
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Regulation of Cell Growth and Death by p53 |
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411 | (18) |
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Regulation of NF-kB Function: Novel Molecular Targets for Pharmacological Intervention |
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429 | (10) |
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Using Protein-Interaction Domains to Manipulate Signaling Pathways |
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439 | (14) |
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Protein Tyrosine Kinase Inhibitors as Novel Therapeutic Agents |
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453 | (14) |
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A Pharmacological Approach to the MAP Kinase Cascade |
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467 | (16) |
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Specific Inhibitors of p38 MAP Kinase |
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483 | (18) |
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Farnesyltransferase Inhibitors: Anti-Ras or Anticancer Drugs? |
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501 | (18) |
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Targeted p53 Gene Therapy-Mediated Radiosensitization and Chemosensitization |
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519 | (18) |
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Treatment of p53-Deficient Cancers by Adenovirus E1B-Region Mutants: From Basic Research to the Clinic |
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537 | (8) |
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The Cell Cycle Inhibitor p27 as a Prognostic Marker in Human Tumors and a Novel Target for Therapeutic Intervention |
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545 | (12) |
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Chemical Cyclin-Dependent Kinase Inhibitors: Therapeutic Implications |
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557 | (11) |
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| Index |
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568 | |