A complementary DNA clone for a macrophage-lymphocyte Fc receptor

Lewis, Victoria; Koch, Terry; Plutner, Helen; Mellman, Ira

doi:10.1038/324372a0

Cited by 162 publications

(87 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recently, several groups reported the cloning and sequencing of macrophage/ lymphocyte FcyR (28)(29)(30). This receptor is composed of two homologous domains, a1 and a2.…”

mentioning

confidence: 99%

An IgE-binding protein with a distinctive repetitive sequence and homology with an IgG receptor.

Albrandt¹,

Orida²,

Liu³

1987

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

View full text Add to dashboard Cite

Proteins that bind IgE play important roles in both the synthesis and function of IgE and are therefore intimately involved in IgE-mediated human allergic disorders. This report describes the structure of an IgE-binding protein, as predicted from sequencing a cDNA cloned from rat basophilic leukemia cells. This protein contains two domains: the amino-terminal domain (140 amino acids) consists of a highly conserved repetitive amino acid sequence, Tyr-Pro-GlyPro/Gln-Ala/Thr-Pro/Ala-Pro-Gly-Ala, whereas the carbox- The IgE receptor on mast cells and basophils has been most extensively studied. Metzger and coworkers (8) have proposed a tetrameric model for this receptor that includes a single highly glycosylated a subunit (Mr, 55,000), a single (3 subunit (Mr, 33,000), and two identical y subunits (Mr, 9000). Kulczycki and coworkers (9-11) have identified a protein of M, 31,000, in addition to the protein equivalent to the a subunit, in a two-cycle affinity purification of rat basophilic leukemia (RBL) cell lysates with IgE immunoadsorbents. A protein of similar properties was also found in rat mast cells (11, 12). Other investigators, using different procedures, have discovered Mr 30,000-33,000 IgE-binding proteins from RBL cells (13). Recently, we have identified a Mr 31,000 protein with affinity for IgE in oocytes injected with mRNA isolated from RBL cells (14) and in the in vitro translation products of RBL mRNA (15). It was shown that this protein exhibits an intrinsic and specific IgE-binding activity and is reactive with a specific rabbit antiserum prepared against highly purified RBL cell proteins isolated by affinity chromatography using IgE immunoadsorbent (9). It was also demonstrated that this IgE-binding protein is expressed specifically in certain cell types known to possess IgE-specific receptors. The cDNA coding for this protein was cloned and the partial amino acid sequence of this protein was determined through DNA sequencing of a partial cDNA (15).We report here the cloning and nucleotide sequence of a full-length cDNA revealing an IgE-binding protein (EBP) containing two distinct structural domains. One of the domains contains a highly conserved repetitive amino acid sequence and the other shares significant sequence homology with the receptor for the Fc portion of IgG (FcyR).t MATERIALS AND METHODSCell Lines and Reagents. The RBL cell line (16) was provided by H. Metzger of the National Institutes of Health. Mouse monoclonal IgE (H1-DNP-e-26.82) and IgG1 (Hi-DNP-y1-109.3) specific for 2,4-dinitrophenyl (DNP) have been described previously (17). Immunoadsorbents were prepared by conjugating 10 mg of protein to 1 g (dry weight) of CNBr-activated Sepharose 4B (Pharmacia).Preparation of RNA. Total cellular RNA was extracted from RBL cells by the guanidinium thiocyanate procedure (18). Isolation of poly(A)+ RNA by oligo(dT)-cellulose affinity chromatography and sucrose density gradient fractionation of the poly(A)+ RNA was performed as described (14).cDNA Cloning, Screening, and Sequencing. ...

show abstract

“…Recently, several groups reported the cloning and sequencing of macrophage/ lymphocyte FcyR (28)(29)(30). This receptor is composed of two homologous domains, a1 and a2.…”

mentioning

confidence: 99%

An IgE-binding protein with a distinctive repetitive sequence and homology with an IgG receptor.

Albrandt¹,

Orida²,

Liu³

1987

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

View full text Add to dashboard Cite

show abstract

“…FcγRIIB are single-chain receptors, encoded by one gene named fcgr2b, which generates two (FcγRIIB1 and FcγRIIB2 in humans) or three (FcγRIIB1, FcγRIIB1' and FcγRIIB2 in mice) isoforms of membrane receptors, by alternative splicing of sequences encoded by the first intracytoplasmic exon (Hibbs et al, 1986;Lewis et al, 1986;Ravetch et al, 1986;Latour et al, 1996). One distinctive feature of the fcgr2b gene is indeed that one exon encodes the transmembrane domain and three others the intracytoplasmic domain of FcγRIIB (in other FcR genes, a single exon encodes both the transmembrane and the intracytoplasmic domains) (Hibbs et al, 1988;Brooks et al, 1989).…”

Section: Inhibitory Fcrsmentioning

confidence: 99%

Negative Signaling in Fc Receptor Complexes

Daëron

Lesourne

2006

Advances in Immunology

View full text Add to dashboard Cite

Cell activation results from the transient displacement of an active balance between positive and negative signaling. This displacement depends in part on the engagement of cell surface receptors by extracellular ligands. Among these are Receptors for the Fc portion of immunoglobulins (FcRs). FcRs are widely expressed by cells of hematopoietic orign. When binding antibodies, FcRs provide these cells with immunoreceptors capable of triggering numerous biological responses in response to specific antigen. FcR-dependent cell activation is regulated by negative signals which are generated together with positive signals within signalosomes that form upon FcR engagement. Many molecules involved in positive signaling, including the FcRβ subunit, the src kinase lyn, the cytosolic adapter Grb2, the transmembrane adapters LAT and NTAL, are indeed also involved in negative signaling. A major player in negative regulation of FcR signaling is the inositol 5-phosphatase SHIP1. Several layers of negative regulation operate sequentially as FcRs are engaged by extracellular ligands of increasing valency. A background protein tyrosine phosphatasedependent negative regulation maintains cells in a « resting » state. SHIP1-dependent negative regulation can be detected as soon as high-affinity FcRs are occupied by antibodies in the absence of antigen. It increases when activating FcRs are engaged by multivalent ligands and, further when FcR aggregation increases, accounting for the bell-shaped dose-response curve observed in excess of ligand. Finally, F-actin skeleton-associated high-molecular weight SHIP1, recruited to phopshorylated ITIMs, concentrates in signaling complexes when activating FcRs are coengaged with inhibitory FcRs by immune complexes. Based on these data, activating and inhibitory FcRs could be used for new therapeutic approaches of immune disorders.

show abstract

“…Exon 2 is an unusually small 21-base-pair (bp) exon encoding amino acids that form part of the signal peptidase recognition site (23,24). The 5' end of exon 3 also participates in coding for the amino acids bor- (3)(4)(5), at least two additional exons must be present, one or more to encode the remainder of the leader peptide and at least one to encode the transmembrane portion with short adjacent intracytoplasmic and extracellular segments (TM).…”

Section: Organization and Sequence Of The Mouse Gene Encodingmentioning

confidence: 99%

“…The gene encoding FcYRIIa is expressed only in macrophages (3,4), and its expression is selectively induced by y interferon (6). The gene encoding FcRIIb is expressed in both macrophages and lymphocytes, with alternative splicing producing two transcripts, b, and b2, which differ only in' their cytoplasmic regions (3)(4)(5). The genes for FcYR that have been cloned (FcRIIa and Fc7RIIb genes) are genetically inseparable from the Mls-i locus on mouse chromosome 1 (9)(10)(11).…”

mentioning

confidence: 99%

“…1 and 2). Interestingly, not only can distinctive Fc receptor genes be expressed on different cell types, but also different spliced messages from the same Fc receptor gene can be expressed in a tissue-specific manner (1)(2)(3)(4)(5)(6). The result of antigen binding to antibody molecules that are bound to different Fc receptors is also dependent upon cell type (1, 2)-e.g., ingestion and processing of antigen in macrophages (6), regulation of antibody synthesis in B cells, and triggering of histamine release from mast cells.…”

mentioning

confidence: 99%

See 1 more Smart Citation