Regulation of signal transduction by the Fc gamma receptor family members and their involvement in autoimmunity.

Abstract	Recent studies on the nature and mode of action of inhibitory receptors and their intracellular phosphatase effector enzymes have identified a new area of research in the etiology of autoimmune diseases. Myeloid cells play a critical role in autoimmunity through their IgG receptors. A number of recent findings reveal that such cells express inhibitory receptors, including the elusive CD32/Fc gamma RIIB isoform, and express inhibitory phosphatases like SHP-1 and SHIP. Animals lacking the effector phosphatases exhibit a pronounced autoimmune and/or pro-inflammatory phenotype. Animals deficient in the expression of the inhibitory receptors often display a much less severe phenotype, likely due to the fact that hematopoietic cells have numerous and probably redundant inhibitory receptors. Genetic deficiencies in the limited number of effector molecules (SHP-1 and SHIP) lead to more dramatic effects on hematopoietic cells and level of inflammation in such animals. These recent findings in animal models open the intriguing possibility that the human homologues of genes encoding the inhibitory receptors like Fc gamma RIIB or effector phosphatases like SHIP might contribute to autoimmune diseases. However, while identification of genes involved in autoimmunity will greatly aid in diagnosis of human autoimmune disease, it is necessary to understand the biochemical mechanisms of action of the numerous inhibitory receptors and phosphatases in the hematopoietic system. Such information will permit the rational design of more efficient and effective treatments for patients. Additional experiments directed at the role and mechanism(s) of action of the inhibitory phosphatases SHP-1 and SHIP will uncover new candidates for diagnosis and treatment of autoimmune diseases.
Authors	K Mark Coggeshall
Journal	Current directions in autoimmunity (Curr Dir Autoimmun) Vol. 5 Pg. 1-29 ( 2002) ISSN: 1422-2132 [Print] Switzerland
PMID	11826753 (Publication Type: Journal Article, Review)
Chemical References	Autoantibodies Immunoglobulin G Intracellular Signaling Peptides and Proteins Receptors, Antigen, B-Cell Receptors, IgG Phosphatidylinositol 3-Kinases Receptor Protein-Tyrosine Kinases src-Family Kinases Phosphoric Monoester Hydrolases PTPN6 protein, human Protein Tyrosine Phosphatase, Non-Receptor Type 6 Protein Tyrosine Phosphatases Ptpn6 protein, mouse INPPL1 protein, human Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases
Topics	Amino Acid Motifs Animals Autoantibodies (immunology) Autoimmune Diseases (immunology) Autoimmunity (immunology) Genes Humans Immunoglobulin G (immunology) Intracellular Signaling Peptides and Proteins Mice Mice, Knockout Myeloid Cells (immunology) Phosphatidylinositol 3-Kinases (physiology) Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases Phosphoric Monoester Hydrolases (physiology) Phosphorylation Protein Processing, Post-Translational Protein Tyrosine Phosphatase, Non-Receptor Type 6 Protein Tyrosine Phosphatases (physiology) Receptor Protein-Tyrosine Kinases (physiology) Receptors, Antigen, B-Cell (immunology) Receptors, IgG (chemistry, genetics, immunology) Signal Transduction (immunology) Structure-Activity Relationship src Homology Domains src-Family Kinases (physiology)

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