The High-Affinity Receptor for Immunoglobulin E

Adamczewski, Martin; Kinét, Jean-Pierre

doi:10.1159/000319254

Cited by 20 publications

(12 citation statements)

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“…Fc⑀RI is a member of a family of receptors expressed on immune effector cells that lack intrinsic enzymatic activity but possess cytoplasmic immune receptor tyrosinebased activation motifs that bind cytoplasmic protein tyrosine kinases (PTKs) (2,3). Similar to other immune cell receptors (such as the T-cell antigen receptor (TCR) or B-cell antigen receptor), Fc⑀RI is composed of multiple subunits including a ligand binding component (␣ chain) noncovalently associated with transmembrane proteins that bear the immune receptor tyrosine-based activation motifs (␤ chain and a homodimer of disulfide-linked ␥ chains) (4,5). The ␤ and ␥ cytoplasmic domains are responsible for signal transduction (6,7).…”

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confidence: 99%

SLP-76 Is a Substrate of the High Affinity IgE Receptor-stimulated Protein Tyrosine Kinases in Rat Basophilic Leukemia Cells

Hendricks-Taylor

Motto

Zhang

et al. 1997

Journal of Biological Chemistry

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Stimulation of the IgE high affinity receptor on rat basophilic leukemia RBL-2H3 cells results in activation of protein tyrosine kinases and rapid tyrosine phosphorylation of several substrates, many of which remain unidentified. In this report, we demonstrate that the Grb2 adapter protein, when expressed as a glutathione S-transferase fusion protein, associates with four tyrosine-phosphorylated molecules (116, 76, 36, and 31 kDa) from lysates of stimulated RBL-2H3 cells. We show further that the 76-kDa protein is SLP-76, a hematopoietic cell-specific protein first identified as a Grb2-binding protein in T cells. Upon stimulation of the high affinity receptor for IgE, SLP-76 undergoes rapid tyrosine phosphorylation and associates with two additional tyrosine phosphoproteins of 62 and 130 kDa via the SH2 domain of SLP-76. Additional studies demonstrate that the SLP-76 SH2 domain also binds a protein kinase from stimulated RBL-2H3 cell lysates. Furthermore, the phosphorylation of SLP-76 requires Syk activity but is not dependent on Ca ؉2 mobilization. These data, together with our previous work documenting its role in T-cell activation, suggest that SLP-76 and the proteins with which it associates may play a fundamental role in coupling signaling events in multiple cell types in the immune system.The high affinity receptor for IgE (Fc⑀RI), 1 found on basophils and mast cells, mediates cell activation in type I allergic reactions (1). Fc⑀RI is a member of a family of receptors expressed on immune effector cells that lack intrinsic enzymatic activity but possess cytoplasmic immune receptor tyrosinebased activation motifs that bind cytoplasmic protein tyrosine kinases (PTKs) (2, 3). Similar to other immune cell receptors (such as the T-cell antigen receptor (TCR) or B-cell antigen receptor), Fc⑀RI is composed of multiple subunits including a ligand binding component (␣ chain) noncovalently associated with transmembrane proteins that bear the immune receptor tyrosine-based activation motifs (␤ chain and a homodimer of disulfide-linked ␥ chains) (4, 5). The ␤ and ␥ cytoplasmic domains are responsible for signal transduction (6, 7). Chimeric receptors containing the cytoplasmic domains and an unrelated extracellular domain mimic most of the cellular signaling events triggered by the intact Fc⑀RI in the rat basophilic leukemia cell line RBL-2H3 (7). Furthermore, stimulation of a chimeric receptor containing the cytoplasmic domain of the TCR chain also results in rat basophilic leukemia cell activation, (8) suggesting a conservation of signaling properties between T cells and mast cells.The interaction of IgE-bound antigens with the Fc⑀RI initiates intracellular signaling events leading to the generation of inflammatory mediators and cytokines. Proximal biochemical events include the rapid phosphorylation and activation of several PTKs including Lyn (a src family kinase) (9), p72-Syk (10, 11), and focal adhesion kinase (12)(13)(14). Lyn associates constitutively with the Fc⑀RI, whereas the interaction between Syk and the ...

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confidence: 99%

SLP-76 Is a Substrate of the High Affinity IgE Receptor-stimulated Protein Tyrosine Kinases in Rat Basophilic Leukemia Cells

Hendricks-Taylor

Motto

Zhang

et al. 1997

Journal of Biological Chemistry

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“…The type I receptor for IgE (FcsRI) is expressed on mast cells and basophils, as well as on Langerhans cells, monocytes, and eosinophils (1). FcsRI clustering on mast cells and basophils initiates a cascade of biochemical processes coupling it to the secretory responses of these cells.…”

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confidence: 99%

“…FcsRI clustering on mast cells and basophils initiates a cascade of biochemical processes coupling it to the secretory responses of these cells. These processes include (i) activation of receptor-associated protein-tyrosine kinases (2) and phosphatases (3), causing transient tyrosine phosphorylation of several cellular proteins (4), (ii) an increase in phosphatidylinositide hydrolysis resulting from phospholipase Cyl activation, and (iii) a rise in the intracellular concentration of free calcium ions (1,5). The final response to this stimulus is secretion of granule-stored mediators and the de novo synthesis and secretion of arachidonic acid metabolites and cytokines.…”

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confidence: 99%

A secretion inhibitory signal transduction molecule on mast cells is another C-type lectin.

Guthmann

Tal

Pecht

1995

Proc. Natl. Acad. Sci. U.S.A.

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Secretion of inflammatory mediators by rat mast cells (line RBL-2H3) was earlier shown to be inhibited upon clustering a membrane glycoprotein by monoclonal antibody G63. This glycoprotein, named mast cell functionassociated antigen (MAFA), was also shown to interfere with the coupling cascade of the type 1 Fce receptor upstream to phospholipase Cy1 activation by protein-tyrosine kinases.Here we report that the MAFA is expressed as both a monomer and a homodimer. initiates a cascade of biochemical processes coupling it to the secretory responses of these cells. These processes include (i) activation of receptor-associated protein-tyrosine kinases (2) and phosphatases (3), causing transient tyrosine phosphorylation of several cellular proteins (4), (ii) an increase in phosphatidylinositide hydrolysis resulting from phospholipase Cyl activation, and (iii) a rise in the intracellular concentration of free calcium ions (1, 5). The final response to this stimulus is secretion of granule-stored mediators and the de novo synthesis and secretion of arachidonic acid metabolites and cytokines. Several membrane components different from the known FcsRI subunits have been identified by specific monoclonal antibodies (mAbs) (6-9) on the rat mucosal-type mast cells (line RBL-2H3) and shown to modulate FcsRI-mediated secretory response. G63, a mAb that binds a membrane glycoprotein, named mast cell function-associated antigen (MAFA), was shown to inhibit the FcsRI-induced signaling cascade upstream to phospholipase Cyl activation (i.e., before phosphatidylinositide hydrolysis and the transient rise in intracellular [Ca2+]), the culminating degranulation (9), and secretion of interleukin 6 (M.D.G. and I.P., unpublished work). The mAb G63 inhibitory effect required MAFA clustering and was not due to interference with IgE-FceRI interactions (9). Still, crosslinking of FcsRI-IgE complexes by multivalent antigen also led to coclustering of the MAFA with the aggregated FceRI and to enhancement of its internalization (9, 10). The MAFA has been identified by immunoprecipitation with mAb G63 as a glycoprotein with a molecular mass of 28-40 kDa on reducing SDS/PAGE (9). We have now pursued its structural characterization' to resolve the basis for its inhibition of immunologically stimulated mast cell secretion. MATERIALS AND METHODSImmunoprecipitation and N-Deglycosylation of MAFA. Cell preparation, surface radioiodination, and lysis were done as described (9). The MAFA was immunoprecipitated with mAb G63-coated beads (2-4 mg of IgG per g of agarose or Affi-Gel). Sedimented beads were either resuspended in deglycosylation buffer (see below) or boiled in SDS/PAGE sample buffer for elution and electrophoresis of bound MAFA. For cleavage of the N-linked oligosaccharide side chains, the sedimented beads were resuspended in 50 ,lI of 10 mM Tris-HCl, pH 7.0/0.1% SDS/0.5% 2-mercaptoethanol and boiled for 5 min. After cooling the mixture to room temperature, 1% Triton X-100, 1 mM EDTA, 2 mM phenylmethylsulfonyl fluoride and N-glycosidas...

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“…Based on these facts, we assume that the IgE immunoglobulin plays an important role in this in vitro bioassay. The rat basophilic leukemia (RBL-2H3) cell line, which originated from mucosa mast cells, has been extensively utilized for the study of the signaling cascade involved in degranulation and inflammatory mediator release (Metzger 1992;Adamczewski and Kinet 1994;Scharenberg and Kinet 1995). These cells rapidly divide in culture; therefore, cell number is not a limitation for signaling studies (Tkaczyk and Gilfillan 2001).…”

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confidence: 99%

Detection of reaginic antibodies against Faenia rectivirgula from the serum of horses affected with Recurrent Airway Obstruction by an in vitro bioassay

et al. 2010

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Reaginic antibodies, mainly of the IgE and some IgG subclasses, play an important role in the induction of type I immediate hypersensitivity reactions. These antibodies bind through their Fc fragment to high affinity receptors (FcεRI) present in the membrane of mast cells and basophils. Previously, several studies have investigated the role of reaginic antibodies in the pathogenesis of RAO. However, whereas immunological aspects of RAO have been extensively studied, the precise sequence of events is still not well understood and role of IgE in this disease still remains controversial. Therefore, in this study a bioassay was developed for reaginic antibody determination in serum from RAO-affected horses in order to determine the etiology of disease. The technique involves measuring in vitro calcium mobilization in RBL-2H3 cells following incubation with horse serum from RAO-affected or unaffected horses and one of the RAO antigens (Faenia rectivirgula). Results demonstrated that 15% of samples from the RAO-affected horses reacted positively in this in vitro bioassay, whereas the samples from unaffected horses did not. This bioassay indicates that reaginic antibodies could be involved in the immunological mechanism leading to RAO; and this technique may facilitate future research in other allergic diseases in horses.

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The High-Affinity Receptor for Immunoglobulin E

Cited by 20 publications

References 0 publications

SLP-76 Is a Substrate of the High Affinity IgE Receptor-stimulated Protein Tyrosine Kinases in Rat Basophilic Leukemia Cells

SLP-76 Is a Substrate of the High Affinity IgE Receptor-stimulated Protein Tyrosine Kinases in Rat Basophilic Leukemia Cells

A secretion inhibitory signal transduction molecule on mast cells is another C-type lectin.

Detection of reaginic antibodies against Faenia rectivirgula from the serum of horses affected with Recurrent Airway Obstruction by an in vitro bioassay

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