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Gene Review

Fcr  -  Fc receptor

Mus musculus

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Disease relevance of Fcr


High impact information on Fcr

  • This restoration of activity does not depend on the tyrosine residues in the beta cytoplasmic tail, implying that antigen receptor-mediated presentation can occur by a pathway distinct from that used by the Fc receptor Fc gamma RIII [6].
  • Mouse macrophages and lymphocytes express two distinct isoforms of a single class of Fc receptor for IgG [7].
  • Prolongation of graft survival is dependent on both complement- and Fc receptor-mediated mechanisms in a major histocompatibility complex (MHC)-mismatched skin transplant model [8].
  • Primary macrophages isolated from mer(kd) mice showed that the phagocytic deficiency was restricted to apoptotic cells and was independent of Fc receptor-mediated phagocytosis or ingestion of other particles [9].
  • These results demonstrate that Fc-receptor-dependent mechanisms contribute substantially to the action of cytotoxic antibodies against tumors and indicate that an optimal antibody against tumors would bind preferentially to activation Fc receptors and minimally to the inhibitory partner FcgammaRIIB [10].

Chemical compound and disease context of Fcr


Biological context of Fcr


Anatomical context of Fcr

  • Polymorphism of Fc receptor on murine B cells is Igh-linked [21].
  • Fc receptor-mediated antibody regulation of T cell immunity against intracellular pathogens [22].
  • These results suggest that the polymorphism in the mitogenic effect of these IgG1 antibodies is caused by polymorphism in monocyte function, possibly at the level of the Fc receptor that reacts with mouse IgG1 [23].
  • The NK cell isoform was not expressed on the surface of COS cells unless cotransfected with a subunit that was expressed in NK cells and that was identical to the gamma subunit of the high affinity IgE Fc receptor (Fc epsilon RI) [24].
  • We found here that the inhibitory Fc receptor FcgammaRIIb was expressed on plasma cells and controlled their persistence in the bone marrow [25].

Associations of Fcr with chemical compounds


Physical interactions of Fcr

  • Results demonstrate the SHIP is the predominant intracellular ligand for the phosphorylated Fc gamma RIIB1 ITIM, although the SHP-2 decoy exhibits some ability to bind Fc gamma RIIB1 and block Fc receptor function [31].
  • Furthermore, suppression was not limited to Fc receptor-mediated phagocytosis because binding and uptake of C3bi-opsonized SRBCs to CR3 receptors was also decreased following LPS treatment [32].
  • A major histocompatibility complex class I-like Fc receptor cloned from human placenta: possible role in transfer of immunoglobulin G from mother to fetus [33].
  • These data indicate that Fc receptor binding of IgG2b results from the concerted action of membrane lipid and protein [34].

Regulatory relationships of Fcr


Other interactions of Fcr

  • Thus, separate receptors mediate these stimulations, and Fc receptor cross-linkage is required for IL-4 production [40].
  • The synthesis and release of CSF-1 and MCP-1 by mesangial cells as a consequence of Fc receptor occupancy may be responsible for macrophage recruitment and activation at sites of immune-complex deposition [41].
  • The increase of mRNA for CSF-1 and MCP-1 was not reduced by either cytochalasin B or D, indicating that Fc receptor occupancy is sufficient for signaling and that phagocytosis is not required to elicit this response [41].
  • Nevertheless, cells derived from PAM cultures in media containing IL-3 displayed a high degree of heterogeneity in terms of their Fc receptor-mediated phagocytic activity [42].
  • Finally, we evaluated the relative importance of the Fc receptor versus the complement pathway in disposing antibody-opsonized DAF/Crry-deficient erythrocytes [43].

Analytical, diagnostic and therapeutic context of Fcr


  1. Fc receptors initiate the Arthus reaction: redefining the inflammatory cascade. Sylvestre, D.L., Ravetch, J.V. Science (1994) [Pubmed]
  2. Uncoupling of immune complex formation and kidney damage in autoimmune glomerulonephritis. Clynes, R., Dumitru, C., Ravetch, J.V. Science (1998) [Pubmed]
  3. Linkage on chromosome 3 of autoimmune diabetes and defective Fc receptor for IgG in NOD mice. Prins, J.B., Todd, J.A., Rodrigues, N.R., Ghosh, S., Hogarth, P.M., Wicker, L.S., Gaffney, E., Podolin, P.L., Fischer, P.A., Sirotina, A. Science (1993) [Pubmed]
  4. Cytotoxic antibodies trigger inflammation through Fc receptors. Clynes, R., Ravetch, J.V. Immunity (1995) [Pubmed]
  5. Redundant and alternative roles for activating Fc receptors and complement in an antibody-dependent model of autoimmune vitiligo. Trcka, J., Moroi, Y., Clynes, R.A., Goldberg, S.M., Bergtold, A., Perales, M.A., Ma, M., Ferrone, C.R., Carroll, M.C., Ravetch, J.V., Houghton, A.N. Immunity (2002) [Pubmed]
  6. Antigen presentation by the B cell antigen receptor is driven by the alpha/beta sheath and occurs independently of its cytoplasmic tyrosines. Patel, K.J., Neuberger, M.S. Cell (1993) [Pubmed]
  7. Fc receptor isoforms exhibit distinct abilities for coated pit localization as a result of cytoplasmic domain heterogeneity. Miettinen, H.M., Rose, J.K., Mellman, I. Cell (1989) [Pubmed]
  8. Fc-dependent depletion of activated T cells occurs through CD40L-specific antibody rather than costimulation blockade. Monk, N.J., Hargreaves, R.E., Marsh, J.E., Farrar, C.A., Sacks, S.H., Millrain, M., Simpson, E., Dyson, J., Jurcevic, S. Nat. Med. (2003) [Pubmed]
  9. Phagocytosis and clearance of apoptotic cells is mediated by MER. Scott, R.S., McMahon, E.J., Pop, S.M., Reap, E.A., Caricchio, R., Cohen, P.L., Earp, H.S., Matsushima, G.K. Nature (2001) [Pubmed]
  10. Inhibitory Fc receptors modulate in vivo cytoxicity against tumor targets. Clynes, R.A., Towers, T.L., Presta, L.G., Ravetch, J.V. Nat. Med. (2000) [Pubmed]
  11. Mac-1 (CD11b/CD18) is crucial for effective Fc receptor-mediated immunity to melanoma. van Spriel, A.B., van Ojik, H.H., Bakker, A., Jansen, M.J., van de Winkel, J.G. Blood (2003) [Pubmed]
  12. Mapping regions of herpes simplex virus type 1 glycoprotein I required for formation of the viral Fc receptor for monomeric IgG. Basu, S., Dubin, G., Nagashunmugam, T., Basu, M., Goldstein, L.T., Wang, L., Weeks, B., Friedman, H.M. J. Immunol. (1997) [Pubmed]
  13. Cyclic AMP modulation of Fc receptor expression on a pre-B cell lymphoma. Burchiel, S.W., Warner, N.L. J. Immunol. (1980) [Pubmed]
  14. Inhibition of the Fc receptor-mediated oxidative burst in macrophages by the Yersinia pseudotuberculosis tyrosine phosphatase. Bliska, J.B., Black, D.S. Infect. Immun. (1995) [Pubmed]
  15. Hemorrhage induces a reduction in the capacity of macrophages to mobilize intracellular calcium secondary to formyl-methionyl-leucyl-phenylalanine stimulation: association with alterations in cells surface Fc receptor expression and increased prostaglandin release. Ayala, A., Chaudry, I.H. Shock (1994) [Pubmed]
  16. CH3 domain of IgG as binding site to Fc receptor on mouse lymphocytes. Ramasamy, R., Secher, D.S., Adetugbo, K. Nature (1975) [Pubmed]
  17. Monoclonal anti-Fc receptor IgG blocks antibody enhancement of viral replication in macrophages. Peiris, J.S., Gordon, S., Unkeless, J.C., Porterfield, J.S. Nature (1981) [Pubmed]
  18. Fc receptor stimulation of phosphatidylinositol 3-kinase in natural killer cells is associated with protein kinase C-independent granule release and cell-mediated cytotoxicity. Bonnema, J.D., Karnitz, L.M., Schoon, R.A., Abraham, R.T., Leibson, P.J. J. Exp. Med. (1994) [Pubmed]
  19. Tyrosine phosphorylation is required for Fc receptor-mediated phagocytosis in mouse macrophages. Greenberg, S., Chang, P., Silverstein, S.C. J. Exp. Med. (1993) [Pubmed]
  20. Activation mediated by RP105 but not CD40 makes normal B cells susceptible to anti-IgM-induced apoptosis: a role for Fc receptor coligation. Yamashita, Y., Miyake, K., Miura, Y., Kaneko, Y., Yagita, H., Suda, T., Nagata, S., Nomura, J., Sakaguchi, N., Kimoto, M. J. Exp. Med. (1996) [Pubmed]
  21. Polymorphism of Fc receptor on murine B cells is Igh-linked. Baum, C.M., McKearn, J.P., Riblet, R., Davie, J.M. J. Exp. Med. (1985) [Pubmed]
  22. Fc receptor-mediated antibody regulation of T cell immunity against intracellular pathogens. Moore, T., Ekworomadu, C.O., Eko, F.O., MacMillan, L., Ramey, K., Ananaba, G.A., Patrickson, J.W., Nagappan, P.R., Lyn, D., Black, C.M., Igietseme, J.U. J. Infect. Dis. (2003) [Pubmed]
  23. Polymorphism in mitogenic effect of IgG1 monoclonal antibodies against T3 antigen on human T cells. Tax, W.J., Willems, H.W., Reekers, P.P., Capel, P.J., Koene, R.A. Nature (1983) [Pubmed]
  24. Mechanisms for regulating expression of membrane isoforms of Fc gamma RIII (CD16). Hibbs, M.L., Selvaraj, P., Carpén, O., Springer, T.A., Kuster, H., Jouvin, M.H., Kinet, J.P. Science (1989) [Pubmed]
  25. FcgammaRIIb controls bone marrow plasma cell persistence and apoptosis. Xiang, Z., Cutler, A.J., Brownlie, R.J., Fairfax, K., Lawlor, K.E., Severinson, E., Walker, E.U., Manz, R.A., Tarlinton, D.M., Smith, K.G. Nat. Immunol. (2007) [Pubmed]
  26. Decreased resistance to bacterial infection and granulocyte defects in IAP-deficient mice. Lindberg, F.P., Bullard, D.C., Caver, T.E., Gresham, H.D., Beaudet, A.L., Brown, E.J. Science (1996) [Pubmed]
  27. In vivo activation of macrophage C3 receptors for phagocytosis. Griffin, F.M., Mullinax, P.J. J. Exp. Med. (1985) [Pubmed]
  28. Purificaton of a functional mouse Fc receptor through the use of a monoclonal antibody. Mellman, I.S., Unkeless, J.C. J. Exp. Med. (1980) [Pubmed]
  29. Regulation of the growth and functions of cloned murine large granular lymphocyte lines by resident macrophages. Minato, N., Amagai, T., Yodoi, J., Diamanstein, T., Kano, S. J. Exp. Med. (1985) [Pubmed]
  30. Differential regulation of B cell development, activation, and death by the src homology 2 domain-containing 5' inositol phosphatase (SHIP). Brauweiler, A., Tamir, I., Dal Porto, J., Benschop, R.J., Helgason, C.D., Humphries, R.K., Freed, J.H., Cambier, J.C. J. Exp. Med. (2000) [Pubmed]
  31. Effects of Src homology domain 2 (SH2)-containing inositol phosphatase (SHIP), SH2-containing phosphotyrosine phosphatase (SHP)-1, and SHP-2 SH2 decoy proteins on Fc gamma RIIB1-effector interactions and inhibitory functions. Nakamura, K., Brauweiler, A., Cambier, J.C. J. Immunol. (2000) [Pubmed]
  32. Lipopolysaccharide-induced suppression of erythrocyte binding and phagocytosis via Fc gamma RI, Fc gamma RII, Fc gamma RIII, and CR3 receptors in murine macrophages. Sundaram, R., O'Connor, M., Cicero, M., Ghaffar, A., Gangemi, J.D., Mayer, E.P. J. Leukoc. Biol. (1993) [Pubmed]
  33. A major histocompatibility complex class I-like Fc receptor cloned from human placenta: possible role in transfer of immunoglobulin G from mother to fetus. Story, C.M., Mikulska, J.E., Simister, N.E. J. Exp. Med. (1994) [Pubmed]
  34. The murine macrophage Fc receptor for IgG2b is lipid dependent. Anderson, C.L. J. Immunol. (1980) [Pubmed]
  35. Mast cell tumor necrosis factor alpha production is regulated by MEK kinases. Ishizuka, T., Terada, N., Gerwins, P., Hamelmann, E., Oshiba, A., Fanger, G.R., Johnson, G.L., Gelfand, E.W. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  36. Rapid induction of CD95 ligand and CD4+ T cell-mediated apoptosis by CD137 (4-1BB) costimulation. Ebata, T., Mogi, S., Hata, Y., Fujimoto, J.I., Yagita, H., Okumura, K., Azuma, M. Eur. J. Immunol. (2001) [Pubmed]
  37. The B cell inhibitory Fc receptor triggers apoptosis by a novel c-Abl family kinase-dependent pathway. Tzeng, S.J., Bolland, S., Inabe, K., Kurosaki, T., Pierce, S.K. J. Biol. Chem. (2005) [Pubmed]
  38. Opposing effects of glucocorticoids on interferon-gamma-induced murine macrophage Fc receptor and Ia antigen expression. Warren, M.K., Vogel, S.N. J. Immunol. (1985) [Pubmed]
  39. T cell activation by anti-CD3 antibodies: function of Fc receptors on B cell blasts, but not resting B cells, and CD18 on the responding T cells. Austyn, J.M., Smith, K.G., Morris, P.J. Eur. J. Immunol. (1987) [Pubmed]
  40. Cross-linking Fc receptors stimulate splenic non-B, non-T cells to secrete interleukin 4 and other lymphokines. Ben-Sasson, S.Z., Le Gros, G., Conrad, D.H., Finkelman, F.D., Paul, W.E. Proc. Natl. Acad. Sci. U.S.A. (1990) [Pubmed]
  41. Receptors for IgG complexes activate synthesis of monocyte chemoattractant peptide 1 and colony-stimulating factor 1. Hora, K., Satriano, J.A., Santiago, A., Mori, T., Stanley, E.R., Shan, Z., Schlondorff, D. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  42. Interleukin-3 (IL-3) stimulates the clonal growth of pulmonary alveolar macrophage of the mouse: role of IL-3 in the regulation of macrophage production outside the bone marrow. Chen, B.D., Mueller, M., Olencki, T. Blood (1988) [Pubmed]
  43. Complement-mediated clearance of erythrocytes: mechanism and delineation of the regulatory roles of Crry and DAF. Decay-accelerating factor. Molina, H., Miwa, T., Zhou, L., Hilliard, B., Mastellos, D., Maldonado, M.A., Lambris, J.D., Song, W.C. Blood (2002) [Pubmed]
  44. The innate mononuclear phagocyte network depletes B lymphocytes through Fc receptor-dependent mechanisms during anti-CD20 antibody immunotherapy. Uchida, J., Hamaguchi, Y., Oliver, J.A., Ravetch, J.V., Poe, J.C., Haas, K.M., Tedder, T.F. J. Exp. Med. (2004) [Pubmed]
  45. The role of nonclassical Fc receptor-associated, Ag-B antigens (Ia) in rat allograft enhancement. Soulillou, J.P., Carpenter, C.B., d'Apice, A.J., Strom, T.B. J. Exp. Med. (1976) [Pubmed]
  46. Molecular basis for a polymorphism of human Fc gamma receptor II (CD32). Warmerdam, P.A., van de Winkel, J.G., Gosselin, E.J., Capel, P.J. J. Exp. Med. (1990) [Pubmed]
  47. In vitro cell-mediated cytotoxicity in primary biliary cirrhosis and chronic hepatitis. Dysfunction of spontaneous cell-mediated cytotoxicity in primary biliary cirrhosis. Vierling, J.M., Nelson, D.L., Strober, W., Bundy, D.M., Jones, E.A. J. Clin. Invest. (1977) [Pubmed]
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