Signaling transduction by IgG receptors

( views:74, downloads:0 )
Journal Title:
Volume 116, Issue 04, 2003
Key Word:
signal transduction;IgG receptors

Abstract: Objective To review and summarize literature regarding stimulatory and inhibitory signaling pathways from different types of Fc gamma receptors (FcγRs).Data source Articles were obtained from Medline from January 1991 to April 2002. Study selection Over 100 English language papers and reviews published over the last 11 years were selected.Results and Conclusions Stimulatory Fcγ receptors include FcγRI, FcγRIIA, FcγRIIC, and FcγRIII A. They transduce signals through the immunoreceptor tyrosine-based activation motif (ITAM) in subunits or in the cytoplasmic domain. Inhibitory Fcγ receptors, such as FcγRIIB, are single chain receptors, transducing signals through an immunoreceptor tyrosine-based inhibitory motif (ITIM) in cytoplasmic domains. Stimulatory signals include protein phosphorylation, increase in intracellular free calcium, the production of 1,4,5-triphosphate inositol (IP3) and diacylglycerol (DAG) mainly through the Src-family kinases, phosphoinositide 3-kinase (PI3-K) and phospholipase C (PLC). Inhibitory signaling has been implicated in the repression of the above activities as well as inhibition of B cell responses through Src homology 2-containing inositol phosphatase (SHIP).

  • [1]Dearon M. Structural basis of FcγR functions. Int Rev Immunol 1997;16:1-27.
  • [2]Cambier JC. Antigen and Fcγ receptor signaling: the awesome power of the immuno-receptor tyrosine-based activation motif. J Immunol 1995;155:3281-3285.
  • [3]Durden DL, Kim HM, Calore B, et al. The FcγRI receptor signals through the activation of hck and MAP kinase. J Immunol 1995;154:4039-4047.
  • [4]Crowley MTCP, Fitzer-Atta CJ, Turner M, et al. A critical role for Syk in signal transduction and phagocytosis mediated by Fcγ receptors on macrophages. J Exp Med 1997;186:1027-1039.
  • [5]Chu J, Liu YB, Koretzky GA, et al. SLP-76-Cbi-Grb2-Shc interactions in FcγRI signaling. Blood 1998;92:1697-1706.
  • [6]Liao F, Shin HS, and Rhee SG. Tyrosine phosphorylation of phospholipase Cγ induced by crosslinking of the high-affinity or low-affinity Fcγ receptor for IgG in U937 cells. Proc Natl Acad Sci U S A 1992;89:3659-3663.
  • [7]Melendez AJ, Bruetschy L, Floto RA, et al. Functional coupling of FcγRI to nicotinamide adenine dinucleotide phosphate (reduced form) oxidative burst and immune complex trafficking requires the activation of phospholipase D1. Blood 2001;98:3421-3428.
  • [8]Melendez AJ, Alirio J, Harnett, et al. Crosstalk between ARF6 and protein kinase C alpha in FcγRI-mediated activation of phospholipase D1. Curr Biol 2001;11:869-874.
  • [9]Floto RA, Somasundaram B, Allen JM, et al. Fcγ receptor I activation triggers a novel Ca2+-activated current selective for monovalent cations in human monocytic cell line U937. J Biol Chem 1997;272:4753-4758.
  • [10]Clark EA, Shattil SJ, Brugge JS. Regulation of protein tyrosine kinase in platelets. Trends Biochem Sci 1994;19:464-469.
  • [11]Mitchell MA, Huang MM, Chien P, et al. Substitutions and deletions in the cytoplasmic domain of the phagocytic receptor FcγRII: effect on receptor tyrosine phosphorylation and phagocytosis. Blood 1994;84:1753-1759.
  • [12]Yanaga F, Poole A, Asselin J, et al. Syk interacts with tyrosine-phosphorylated proteins in human platelets activated by collagen and crosslinking of the Fcγ-IIA receptor. Biochem J 1995;311:471-478.
  • [13]Pain S, Falet H, Saci A, et al. Tyrosine phosphorylation and association of FcγRII and p72(Syk) are not limited to the FcγRII signalling pathway. Cell Signal 2000;12:165-171.
  • [14]Chacko GW, Brandt JT, Coggeshall KM, et al. Phosphoinositide 3-kinase and p72syk non-covalently associate with the low affinity Fcγ receptor on human platelets through an immunoreceptor tyrosine-based activation motif. J Biol Chem 1996;271:10775-10781.
  • [15]Saci A, Pain S, Rendu F, et al. Fcγ receptor-mediated platelet activation is dependent on phosphatidylinositol 3-kinase activation and involves p120(Cbl). J Biol Chem 1999;274:1898-1904.
  • [16]Robinson A, Gibbins J, Rodriguez-Linares B, et al. Characterization of Grb2-binding proteins in human platelets activated by FcγRIIA crosslinking. Blood 1996;88:522-530.
  • [17]Anderson GP, Anderson CL. Signal transduction by the platelet Fcγ receptor. Blood 1990;76:1165-1172.
  • [18]Gratacap MP, Payrastre B, Viala C, et al. Phosphatidylinositol 3,4,5-trisphosphate-dependent stimulation of phospholipase C-γ2 is an early key event in FcγRIIA-mediated activation of human platelets. J Biol Chem 1998;273:24314-24321.
  • [19]Gratacap MP, Herautt JP, Viala C, et al. FcγRIIA requires a Gi-dependent pathway for an efficient stimulation of phosphoinositide 3-kinase, calcium mobilization, and platelet aggregation. Blood 2000;96:3439-3446.
  • [20]Agarwal A, Salem P, Robins KC. Involvement of p72syk, a protein-tyrosine kinase, in Fcγ receptor signaling. J Biol Chem 1993;268:15900-15905.
  • [21]Cooney DS, Phee H, Jacob A, et al. Signal transduction by human-restricted FcγRIIa involves three distinct cytoplasmic kinase families leading to phagocytosis. J Immunol 2001;167:844-854.
  • [22]Renedo MA, Fernández N, Sánchez Crespo M. FcγRIIA exogenously expressed in HeLa cell activates the mitogen-activated protein kinase cascade by a mechanism dependent on the endogenous expression of the protein tyrosine kinase Syk. Eur J Immunol 2001;31:1361-1369.
  • [23]Coxon PY, Rane MJ, Powell DW, et al. Differential mitogen-activated kinase stimulation by Fcγ receptor IIa and Fcγ receptor IIIb determines the activation phenotype of human neutrophils. J Immunol 2000;164:6530-6537.
  • [24]Gergely J and Sarmay G. FcγRII-Mediated regulation of human B cells. Scand J Immunol 1996;44:1-10.
  • [25]Diegel ML, Rankin BM, Bolen JB, et al. Crosslinking of Fcγ receptor to surface immunoglobulin on B cells provides an inhibitory signal that closes the plasma membrane calcium channel. J Biol Chem 1994;269:11409-11416.
  • [26]Pani G, Kozlowski M, Cambier JC, et al. Identification of the tyrosine phosphatase PTP1C as a B cells antigen receptor-associated protein involved in the regulation of B cell signaling. J Exp Med 1995;181:2077-2084.
  • [27]TaKai T, Ono M, Kikida M, et al. Augmented humoral and anaphylactic responses in II-deficent mice. Nature 1996;379:346-349.
  • [28]Muta T, Kurosaki T, Misulokin Z, et al. A 13-amino acid motif in the cytoplasmic domain of FcγRIIB modulates B cell receptor signaling. Nature 1994;368:70-73.
  • [29]Fong DC, Brauweiler A, Minskoff SA, et al. Mutational analysis reveals multiple distinct sites within Fcγ receptor IIB that function in inhibitory signaling. J Immunol 2000; 165:4453-4462.
  • [30]Chen T, Zimmermann W, parker J, et al. Biliary glycoprotein (BGPa, CD66a, CEACAM1) mediates inhibitory signals. J Leukoc Biol 2001;70:335-340.
  • [31]D'Ambrosio D, Hippen Kl, Miskoff SA, et al. Recruitment and activation of PTP1C in negative regulation of antigen receptor signaling by FcγRIIB1. Science 1995;268:293-297.
  • [32]Nadler MJS, Chen B, Anderson JS, et al. Protein-tyrosine phosphatase SHP-1 is dispensable for FcγRIIB-mediated inhibition of B cell antigen receptor activation. J Biol Chem 1997;272:20038-20043.
  • [33]Ono M, Okada H, Bollands, et al. Detection of SHIP or SHP-1 reveals two distinct pathways for inhibitory signaling. Cell 1997;90:293-301.
  • [34]Ono M, Bolland S, Tempst P, et al. Role of the inositol phosphatase SHIP in negative regulation of the immune system by the receptor FcγRIIB. Nature 1996;382:263-266.
  • [35]Sato K, Ochi A. Superclustering of B cell receptor and FcγRIIB1 activate Src homology 2-containing protein tyrosine phosphatase-1. J Immunol 1998;161:2716-2722.
  • [36]Brauweiler AM, Tamir I, Cambier JC. Bilevel control of B-cell activation by the inositol 5-phophatase SHIP. Immunol Rev 2000;176:69-74.
  • [37]Nakamura K, Cambier JC. B cell antigen receptor (BCR)-mediated formation of a SHP-2-p120 complex and its inhibition by FcγRIIB1-BCR co-ligation. J Immunol 1998;161:684-691.
  • [38]Liu Q, oliveira-Dos-Santos AJ, Mariathasan S, et al. The inositol polyphosphate 5-phosphatase SHIP is a crucial negative regulator of B cell antigen receptor signaling. J Exp Med 1998;188:1333-1342.
  • [39]Brauweiler A, Tamir I, Dal Porto J, et al. Differential regulation of B cell development, activation, and death by the src homology 2 domain-containing 5' inositol phospatase (SHIP). J Exp Med 2000;191:1545-1554.
  • [40]Hegason CD, Kalberer C, Damen JE, et al. A dual role for SHIP in immunity aberrant development and enhanced function of B lymphocytes in SHIP-/- mice. J Exp Med 2000;191:781-794.
  • [41]Phee H, Rodgers W, Coggeshall, et al. Visualization of inhibitory signaling in B cells by quantitative confocal microscopy. Mol Cell Biol 2001;21:8615-8625.
  • [42]Kato I, Takai T, Kudo A, et al. The pre-B cell receptor signaling for apoptosis is negatively regulated by Fc gamma RIIB. J Immunol 2002;168:629-634.
  • [43]Yamanashi Y, Tamura T, Kanamori T, et al. Role of the ras GAP-associated docking protein p62(dok) in negative regulation of B cell receptor-mediated signaling. Genes Dev 2000;14:11-16.
  • [44]Tamir I, Stolpa JC, Helgason CD, et al. The Ras GAP-binding protein p62Dok is a mediator of inhibitory FcγRIIB signals in B cells. Immunity 2000;12:347-358.
  • [45]Tridandapani S, Chacko GK, Van Brocklyn JR, et al. Inhibitory signaling in B cells causes reduced Ras activity by reducing Shc-Grb2 interactions. J Immunol 1997;158:1125-1132.
  • [46]Harmer SL, DeFranco AL. The src homology domain 2-containing inositol phosphatase SHIP forms a ternary comlex with Shc and Grb2 in antigen receptor-stimullated B lymphocytes. J Biol Chem 1999;274:12183-12191.
  • [47]Deuter-Reinhard M, Apell G, Pot D, et al. SIP/SHIP inhibits Xenopus oocyte maturation induced by insulin and phosphatidylinositol 3-kinase. Mol Cell Biol 1997;17:2559-2565.
  • [48]Choquet D, Partiseti M, Amigorena S, et al. Crosslinking of IgG receptors inhibits membrane immunolglobulin-stimulated calcium influx in B lymphocytes. J Biol Chem 1993;121:355-363.
  • [49]Sarkar S, Schlottmann K, Cooney D, et al. Inhibitory signaling via FcγRIIB1 in B cells blocks phopspholipase Cγ2 phosphorylation but not Syk or Lyn activation. J Biol Chem 1996;271:20182-20186.
  • [50]Kiener PA, Lionbin MN, and Rohrschnoider LR, et al. Co-ligation of the antigen and Fcγ receptors gives rise to the selective modulation of intracellular signaling in B cells. J Biol Chem 1997;272:3838-3844.
  • [51]Nakamura K, Brauweiler A, Cambier JC. Effects of Src homology domain 2 (SH2)-containing inositol phosphatase (SHIP), SH2-containing phosphtyrosine phosphatase (SHP)-1, and SHP-2 SH2 decoy proteins on FcγRIIB1-effector interactions and inhibitory functions. J Immunol 2000;164:631-638.
  • [52]Jacob A, Cooney D, Tridandapani S, et al. FcγRIIB modulation of surface immunoglobulin-induced Akt activation in murine B cells. J Biol Chem 1999;274:13704-13710.
  • [53]Malbec O, Schmitt C, Bruhns P, et al. Src homology 2 domain-containing inositol 5-phosphatase 1 mediates cell cycle arrest by FcγRIIB. J Biol Chem 2001;276:30381-30391.
  • [54]Muraille E, Bruhns P, Pesesse X, et al. The SH2 domain containing inositol 5-phosphatase SHIP2 associates to the immunoreceptor tyrosine-based inhibition motif of FcγRIIB in B cells under inhibitory signaling. Immunol Lett 2000;72:7-15.
  • [55]Bruhns P, Vely F, Malbec O, et al. Molecular basis of the recruitment of the SH2 domain-containing inositol 5-phosphatases SHIP1 and SHIP2 by FcγRIIB. J Biol Chem 2000;275:37357-37364.
  • [56]Wisniewski D, Strif A, Swendeman S, et al. A novel SH2-containing phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase (SHIP2) is constitutively tyrosine phosphorylated and asocciated with src homologous and collagen gene (SHC) in chronic myelogenous leukemia progenitor cells. Blood 1999;93:2707-2720.
  • [57]Celement S, Kraus U, Desmedt F, et al. The lipid phosphatase SHIP2 controls insulin sensitivity. Nature 2001;409:92-97.
  • [58]Brauweiler A, Tamir I, Marschner S, et al. Partially distinct molecualr mechanism mediate inhibitory FcγRIIB signaling in resting and activated B cells. J Immunol 2001;167:204-211.
  • [59]O'Shea JJ, Weissman AM, Kennedy ICS, et al. Engagement of the natural killer cell IgG Fcγ receptor results in tyrosine phosphorylation of the zeta chain. Proc Natl Acad Sci U S A 1991;88:350-354.
  • [60]Milella M, Gismondi A, Roncaioli P, et al. Beta 1 integrin crosslinking inhibits CD16-induced phospholipase D and secretory phospholipase A2 activity and granule exocytosis in human NK cells:role of phospholipase D in CD16-triggered degranulation. J Immunol 1999;162:2064-2072.
  • [61]Liao F, Hyun SS, Rhee SG. Crosslinking of FcγRIIIA on natural killer cells results in tyrosine phosphorylation of PLC-γ1 and PLC-γ2. J Immunol 1993;150:2668-2674.
  • [62]Azzoni L, Kamoun M, Salcedo TW, et al. Stimulation of FcγRIIIA results in phospholipase Cγ1 tyrosine phosphorylation and p56lck activation. J Exp Med 1992;176:1745-1750.
  • [63]Stahl A, Liwszyc GE, Couture C, et al. Trigger of human natural killer cells through CD16 induces tyrosine phosphorylation of the p72syk kinase. Eur J Immunol 1994;24:2491-2496.
  • [64]Galandrini R, Palmieri G, Piccoli M, et al. CD16-mediated p21ras activation is associated with Shc and p36 tyrosine phosphorylation and their binding with Grb2 in human natural killer cells. J Exp Med 1996;183:179-186.
  • [65]Kanakaraj P, Duckworth B, Azzoni L, et al. Phosphatidylinositol 3-kinase activation induced upon FcγRIIIA-ligand interaction. J Exp Med 1994;179:551-558.
  • [66]Galandrini R, Palmieri G, Palmieri G, et al. Role for the Rac1 exchange factor Vav in the signaling pathways leading to NK cell cytotoxicity. J Immunol 1999;162:3148-3152.
  • [67]Jevremovic D, Billadeau DD, Schoon RA, et al. Regulation of NK cell-mediated cytotoxicity by the adaptor protein 3BP2. J Immunol 2001;166:7219-7228.
  • [68]Milella M, Gismondi A, Roncaioli P, et al. CD16 crosslinking induces both secretory and extracellular signal-regulated kinase (ERK)-dependent cytosolic phospolipase A2 (PLA2) activity in human natural killer cells. J Immunol 1997;158:3148-3154.
  • [69]Zhou MJ, Lublin DM, Link DC, et al. Distinct tyrosine kinase activation and Triton X-100 insolubility upon FcγRII or FcγRIIIB ligation in human polymorphonuclear leuckocytes. J Biol Chem 1995;270:13553-13560.
  • [70]Hoffmeyer F, Witte K, Gebbardt U, et al. The low affinity FcγRIIa and FcγRIIIb on polymorphonuclear neutrophils are differently regulated by CD45 phosphatase. J Immunol 1995;155:4016-4023.
  • [71]Hundt M Schmidt RE. The glycosylphosphatidylinositol-linked Fcγ receptor III represents the dominant receptor structure for immune complex activation of neutrophils. Eur J Immunol 1992;22:811-816.
  • [72]Vossebeld PJ, Kessler J, von dem Borne AE, et al. Heterotypic FcγR clusters evoke a synergistic Ca2+ response in human neutrophils. J Biol Chem 1995;270:10671-10679.
  • [73]Watson F, Gasmi L, Edwards SW. Stimulation of intracellular Ca2+ levels in human neutrophils by soluble immune complexes. J Biol Chem 1997;272:17944-17951.
  • [74]Hazan-Halevy I, Seger R, Levy R. The requirement of both extracellular regulated kinase and p38 mitogen-activated protein kinase for stimulation of cytosolic phopholipase A2 activity by either FcγRIIA or FcγRIIIB in human neutrophils. J Biol Chem 2000;275:12416-12423.
WanfangData CO.,Ltd All Rights Reserved
About WanfangData | Contact US
Healthcare Department, Fuxing Road NO.15, Haidian District Beijing, 100038 P.R.China
Tel:+86-010-58882616 Fax:+86-010-58882615