Signal Transduction in Mast Cells and Basophils

Section I.- 1 Signals in the Regulation of Mast Cell Growth and Development: A Perspective.- Mast Cells: Versatile Effector Cells in Health and Disease.- Mast Cell Development: A Brief Overview.- In Vivo Veritas: In Vitro Versus In Vivo Models of Mast Cell Development.- Mice or Humans? Species Differences in Mast Cell Development and Phenotype.- Conclusions.- 2 The Regulation of Mast Cell and Basophil Development by the Kit Ligand, SCF, and IL-3.- Discovery of SCF, a Ligand for the Receptor Encoded at c-kit.- Effects of SCF in Mast Cell Biology.- Recombinant Human SCF Promotes Human Mast Cell Hyperplasia In Vivo.- SCF/Kit Signaling and the Regulation of the Survival and Size of Mast Cell Populations In Vivo.- SCF Can Regulate Mast Cell Secretory Function.- Interleukin-3.- Assessing the Role of IL-3 in Mouse Mast Cell and Basophil Development Using IL-3 -/- Mice.- KitW/KitW-v, IL-3 -/- Mice Exhibit a Profound Impairment of Mucosal Mast Cell Development and Immunity, During Infection with Strongyloides venezuelensis.- SCF and IL-3 Have Distinct Roles in the Regulation of Physiological Mast Cell and Basophil Development and Immunologically Induced Mast Cell and Basophil Hyperplasia.- Conclusions.- 3 The c-kit Receptor and the mi Transcription Factor: Two Important Molecules for Mast Cell Development.- Kit.- MITF.- Conclusions.- 4 Mouse and Rat Models of Mast Cell Development.- Identification of the Major Granule Constituents of Mouse MC.- Granule Characterization of Varied Populations of MC in Normal Mice.- Helminth-Induced Mastocytosis in the Jejunum.- mBMMC.- Transformed MC Lines.- Future Directions.- 5 Factors That Affect Human Mast Cell and Basophil Growth.- Ontogeny of Mast Cells and Basophils.- General Characteristics of Mast Cells and Basophils.- Mast Cell Phenotypes In Vivo.- Development In Vitro of Human Basophils and Mast Cells.- In Vitro Studies on Mast Cells and Basophils Utilizing Cell Lines.- Development of Human Mast Cells and Basophils In Vivo.- Conclusions.- 6 Signal Transduction by Cytokines.- Mast Cells and Cytokines.- The Four-Helix Bundle Cytokine Family.- Interferons and IL-10.- Tyrosine Phosphorylation Events.- Activation of Ras Proteins.- Tyrosine Phosphorylation of She and Its Function as an Adaptor.- MAP Family Kinases.- Functions of MAP Family Kinases in Mast Cells.- The IL-4 and IL-13 Receptors.- Similarities and Differences in Signal Transduction by Different Cytokines.- Conclusions.- 7 Mast Cell Apoptosis and Its Regulation.- Physical Triggers of Mast Cell Apoptosis.- Cytokines Regulating Mast Cell Apoptosis.- Genetic Control of Mast Cell Apoptosis.- Mast Cell Apoptosis In Vivo: Clinical Correlates.- Conclusions.- Section II.- 8 Early Signals in Mast Cell Activation: A Perspective.- Role of Aggregation: Two Models.- Ligand Affinity and Signaling.- Conclusions.- 9 Fc?RI Signaling in Specialized Membrane Domains.- Background.- Fc?RI Activation in Membrane Domains.- Future Directions.- Conclusions.- 10 Regulation and Function of Protein Tyrosine Kinase Syk in Fc?RI-Mediated Signaling.- Protein Tyrosine Phosphorylation.- Importance of Syk in Cellular Signaling.- Present Model for Early Events in Fc?RI Signaling.- Structure of Syk.- Regulation of the Function of Syk.- Association of Syk with Other Proteins.- Downstream Molecules: Substrates.- Conclusions.- 11 The Role of Protein Phosphatases in Cell Signaling by the High-Affinity Receptor for Immunoglobulin E.- Protein Tyrosine Phosphatases.- Phosphatase-Dependent Inhibitory Receptors.- Protein Serine/Threonine Phosphatases.- General Considerations.- 12 Protein Kinase C and Early Mast Cell Signals.- Molecular Structure of PKC Family Members.- Translocation and Activation of PKC Isozymes.- Regulation of PKC Activity.- PKC, the Mast Cell, and the Basophil.- Activation of PKC in the Mast Cell: Is Activation an Early Event?.- PKC and Receptor Phosphorylation.- Molecular Associations of PKC In Vivo.- Protein Kinase C: A Suitable Target for Therapeutic Intervention?.- Conclusions.- 13 Mast Cell Inhibitory Receptors of the Immunoglobulin Superfamily.- Mast Cell Fc?RIIb 172].- Mouse gp49B1/Human HL9.- Mast Cell p91 and PIR-B1.- Functional Implications of Multiple ITIM-Bearing Inhibitory Receptors in Mast Cells.- Section III.- 14 Signaling Pathways That Regulate Effector Function: Perspectives.- Model of Pathways Activated by Fc?RI Aggregation.- Binding of Negatively Regulating Molecules to Fc?RI and Their Tyrosine Phosphorylation Independent of Syk.- Cell Adhesion, Focal Adhesion Kinases, and Signaling.- Conclusions.- 15 Phosphoinositide-Derived Second Messengers in Fc?RI Signaling: PI-3 Kinase Products Control Membrane Topography and the Translocation and Activation of PLC-?1 in Antigen-Stimulated Mast Cells.- Phosphatidylinositol 3-Kinase.- Phospholipase ?.- PI-3 Kinase Controls the Translocation and Activation of PLC-?1.- Conclusions.- 16 Phospholipase D and Its Role in Mast Cells.- Catalytic Reactions and Assays of PLD: Phospholipid Hydrolysis and Transphosphatidylation.- Biochemical Characteristics and Regulation of PLD.- Cloned PLD Isoforms.- Pharmacological Probes for Study of PLD Function.- Physiological Roles of PLD.- PLD in Mast Cells.- Unanswered Questions and Conclusions.- Addendum.- 17 New Perspectives on Ca2+ Influx in Mast Cells.- Historical Frame of Reference.- Practical Lessons from the Past.- Properties of an Antigen-Evoked Ca2+ Current in RBL-2H3 Cells.- Measurements of Ca2+ Current Versus 45Ca2+ Influx.- Benefits of Noninvasive Measurements at Warm Temperatures.- Future Directions.- Ca2+-Dependent Activation of NF-AT by the Fc?RI.- Conclusions.- 18 The MAP Kinases and Their Role in Mast Cells and Basophils.- The MAP Kinases.- MAP Kinases in Mast Cells.- Conclusions.- 19 Tec Family Protein Tyrosine Kinases and Their Interaction with Protein Kinase ?.- Structure of Tec Family PTKs.- Function of Tec Family PTKs.- PH Domains.- Perspectives.- 20 Activation of Heterotrimeric GTP-Binding Proteins.- The Supergene Family of GTP-Binding Proteins.- Tools to Study G-Protein Functions.- Direct Evidence for the Involvement of GTP-Binding Proteins in Mast Cell Exocytosis.- G Proteins as Mediators of the Peptidergic Pathway of Mast Cell Activation.- G Proteins Are the Cellular Receptors of Basic Secretagogues.- Activation of Mast Cell Exocytosis by the Heterotrimeric G Protein Gi3.- The Involvement of Ctx-Sensitive G Proteins in Mast Cell Signaling.- The Role of G?z in Mediating Fc?RI-Induced Responses.- Future Perspectives.- 21 Activation of Small GTP-Binding Proteins.- Ras.- Rab.- ARF.- Rho.- Conclusions.- Section IV.- 22 Regulation of Mediator Synthesis and Secretion: Overview.- 23 Early-Response Genes in Mast Cell Activation.- PKC and Mast Cell Proliferation.- AP-1 in Activated Mast Cells.- PKC and AP-1 in Activated Mast Cells.- USF-2 in Mast Cells.- Microphthalmia Transcription Factor (mi) in Mast Cells.- 24 Fc?RI-Mediated Activation of NF-AT.- Transcription Factors in Mast Cells.- NF-AT-Like Factors in Mast Cells.- NF-AT Factor(s) and Cofactors in Mast Cells.- NF-AT DNA-Binding Sites in Mast Cells.- NF-AT Activation in Mast Cells via the MAP Kinase Pathway.- NF-AT Activation via Calcineurin.- Signal Pathways That Do Not Link the Fc?RI to NF-AT, the PKC Pathway, and the PI-3 Kinase Pathway.- 25 Regulation of IL-4 Expression in Mast Cells.- The Role of Interleukin-4 in Immunity.- Signaling Events Resulting in Cytokine Transcription.- Transcriptional Regulation of Interleukin-4.- Conclusions.- 26 Arachidonic Acid Metabolism in Mast Cells.- Phospholipase A2 Enzymes.- Prostaglandin Generation.- Leukotriene Generation.- Arachidonic Acid Metabolism in Mast Cells.- Conclusions.- 27 Role of ICRAC in the Regulation of Secretion.- Stimulus-Secretion Coupling in Mast Cells.- Calcium Dependence of Secretion.- Regulation of ICRAC and Consequences for Secretion.- 28 Regulation of Secretion in Human Basophils.- Intrinsic Regulation of Secretion.- Regulation by Extrinsic Factors.- Summary.- 29 Histamine Releasing Factors.- History.- Interleukins.- Chemokines.- The IgE-Dependent HRF.- Clinical Relevance of HRF.- Conclusions.