Fc gamma RIIB as a potential molecular target for intravenous gamma globulin therapy. 2001

V L Ott, and D C Fong, and J C Cambier
Department of Immunology, University of Colorado Health Sciences Center, Denver, USA.

The ability of the immune system to respond appropriately to foreign antigen is dependent on a delicate balance of activating and inhibitory signals. Recently, the role of cell surface inhibitory receptors in attenuating immune responses, thereby preventing pathologic conditions including autoimmunity and atopy, has been recognized. It is postulated that the beneficial effects of intravenous gamma globulin in the treatment of immune disorders may be attributable, at least in part, to engagement of Fc gamma RIIB, a member of the recently described family of immune inhibitory receptors. Recent genetic and biochemical studies have identified the SH2 domain-containing inositol 5-phosphatase (SHIP) as a critical effector in Fc gamma RIIB inhibitory signaling. This review summarizes recent work from our laboratory and others aimed to define the mechanism(s) by which Fc gamma RIIB and its effector, SHIP, inhibit immune responses. Elucidation of these mechanisms may lead to the development of therapeutic strategies for the treatment of autoimmune and inflammatory pathologies that specifically target Fc gamma RIIB or its effector(s).

UI MeSH Term Description Entries
D008954 Models, Biological Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment. Biological Model,Biological Models,Model, Biological,Models, Biologic,Biologic Model,Biologic Models,Model, Biologic
D010744 Phosphoric Monoester Hydrolases A group of hydrolases which catalyze the hydrolysis of monophosphoric esters with the production of one mole of orthophosphate. Phosphatase,Phosphatases,Phosphohydrolase,Phosphohydrolases,Phosphomonoesterase,Phosphomonoesterases,Phosphoric Monoester Hydrolase,Hydrolase, Phosphoric Monoester,Hydrolases, Phosphoric Monoester,Monoester Hydrolase, Phosphoric
D005719 gamma-Globulins Serum globulins that migrate to the gamma region (most positively charged) upon ELECTROPHORESIS. At one time, gamma-globulins came to be used as a synonym for immunoglobulins since most immunoglobulins are gamma globulins and conversely most gamma globulins are immunoglobulins. But since some immunoglobulins exhibit an alpha or beta electrophoretic mobility, that usage is in decline. gamma-Globulin,gamma Globulin,gamma Globulins
D000072183 Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases Phosphoinositide phosphatases that catalyze the dephosphorylation (hydrolysis) of phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5)P(3)) to produce PtdIns(3,4)P(2), which negatively regulates the PI3K ( 3-PHOSPHOINOSITIDE-DEPENDENT PROTEIN KINASES) pathways. They contain an SH2 DOMAIN and STERILE ALPHA MOTIF and have important functions in regulating the immune response and other cellular processes in vertebrates. SHIP Phosphatases,Src Homology 2 Domain-Containing Inositol Phosphatases,Phosphatases, SHIP,Src Homology 2 Domain Containing Inositol Phosphatases
D015398 Signal Transduction The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. Cell Signaling,Receptor-Mediated Signal Transduction,Signal Pathways,Receptor Mediated Signal Transduction,Signal Transduction Pathways,Signal Transduction Systems,Pathway, Signal,Pathway, Signal Transduction,Pathways, Signal,Pathways, Signal Transduction,Receptor-Mediated Signal Transductions,Signal Pathway,Signal Transduction Pathway,Signal Transduction System,Signal Transduction, Receptor-Mediated,Signal Transductions,Signal Transductions, Receptor-Mediated,System, Signal Transduction,Systems, Signal Transduction,Transduction, Signal,Transductions, Signal
D015703 Antigens, CD Differentiation antigens residing on mammalian leukocytes. CD stands for cluster of differentiation, which refers to groups of monoclonal antibodies that show similar reactivity with certain subpopulations of antigens of a particular lineage or differentiation stage. The subpopulations of antigens are also known by the same CD designation. CD Antigen,Cluster of Differentiation Antigen,Cluster of Differentiation Marker,Differentiation Antigens, Leukocyte, Human,Leukocyte Differentiation Antigens, Human,Cluster of Differentiation Antigens,Cluster of Differentiation Markers,Antigen Cluster, Differentiation,Antigen, CD,CD Antigens,Differentiation Antigen Cluster,Differentiation Marker Cluster,Marker Cluster, Differentiation
D016756 Immunoglobulins, Intravenous Immunoglobulin preparations used in intravenous infusion, containing primarily IMMUNOGLOBULIN G. They are used to treat a variety of diseases associated with decreased or abnormal immunoglobulin levels including pediatric AIDS; primary HYPERGAMMAGLOBULINEMIA; SCID; CYTOMEGALOVIRUS infections in transplant recipients, LYMPHOCYTIC LEUKEMIA, CHRONIC; Kawasaki syndrome, infection in neonates, and IDIOPATHIC THROMBOCYTOPENIC PURPURA. Antibodies, Intravenous,Human Intravenous Immunoglobulin,IV Immunoglobulin,IVIG,Intravenous Antibodies,Intravenous Immunoglobulin,Intravenous Immunoglobulins,Alphaglobin,Endobulin,Flebogamma DIF,Gamimmune,Gamimmune N,Gamimune,Gamimune N,Gammagard,Gammonativ,Gamunex,Globulin-N,IV Immunoglobulins,Immune Globulin Intravenous (Human),Immune Globulin, Intravenous,Immunoglobulins, Intravenous, Human,Intraglobin,Intraglobin F,Intravenous IG,Intravenous Immunoglobulins, Human,Iveegam,Modified Immune Globulin (Anti-Echovirus Antibody),Privigen,Sandoglobulin,Venimmune,Venoglobulin,Venoglobulin-I,Globulin N,Human Intravenous Immunoglobulins,Immunoglobulin, Human Intravenous,Immunoglobulin, IV,Immunoglobulin, Intravenous,Immunoglobulins, Human Intravenous,Immunoglobulins, IV,Intravenous Immune Globulin,Intravenous Immunoglobulin, Human,Venoglobulin I
D017452 Receptors, IgG Specific molecular sites on the surface of various cells, including B-lymphocytes and macrophages, that combine with IMMUNOGLOBULIN Gs. Three subclasses exist: Fc gamma RI (the CD64 antigen, a low affinity receptor), Fc gamma RII (the CD32 antigen, a high affinity receptor), and Fc gamma RIII (the CD16 antigen, a low affinity receptor). Antigens, CD16,Antigens, CD32,Antigens, CD64,CD16 Antigens,CD32 Antigens,CD64 Antigen,CD64 Antigens,Fc Gamma Receptor,Fc Receptors, gamma,Fc gamma Receptors,IgG Receptor,IgG Receptors,Leu-11 Antigen,Receptors, Fc gamma,gamma Fc Receptor,gamma Fc Receptors,CD 16 Antigens,CD 32 Antigens,CD 64 Antigens,CDw32 Antigens,Fc gamma RI,Fc gamma RII,Fc gamma RIII,Immunoglobulin G Receptor,Leu-11 Antigens,Antigen, CD64,Antigen, Leu-11,Antigens, CD 16,Antigens, CD 32,Antigens, CD 64,Antigens, CDw32,Antigens, Leu-11,Fc Receptor, gamma,Gamma Receptor, Fc,Leu 11 Antigen,Leu 11 Antigens,Receptor, Fc Gamma,Receptor, IgG,Receptor, Immunoglobulin G,Receptor, gamma Fc,Receptors, gamma Fc,gamma RI, Fc,gamma RII, Fc,gamma RIII, Fc,gamma Receptors, Fc
D018909 src Homology Domains Regions of AMINO ACID SEQUENCE similarity in the SRC-FAMILY TYROSINE KINASES that fold into specific functional tertiary structures. The SH1 domain is a CATALYTIC DOMAIN. SH2 and SH3 domains are protein interaction domains. SH2 usually binds PHOSPHOTYROSINE-containing proteins and SH3 interacts with CYTOSKELETAL PROTEINS. SH Domains,SH1 Domain,SH2 Domain,SH3 Domain,src Homology Region 2 Domain,Homology Domain, src,Homology Domains, src,SH Domain,SH1 Domains,SH2 Domains,SH3 Domains,src Homology Domain

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