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Blood, 1 June 2003, Vol. 101, No. 11, pp. 4479-4484
Fc
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Abstract |
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 Top Abstract IntroductionMaterials and methodsResultsDiscussionReferences |
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chain–dependent Fc receptors FcRIIIA and FcRI. FcR chimeras containing the TM and cytoplasmic (CY) domains of the chain were expressed on the cell surface and mediated an efficient phagocytic signal. In contrast, chimeras containing the FcRIIIA TM were poorly expressed. Receptors containing the FcRI TM and the chain CY but lacking the chain TM also were expressed efficiently and mediated phagocytosis, suggesting that a chain dimer induced by the chain TM is not required for efficient phagocytosis. Cotransfection of FcRI or FcRIIIA with the chimera CD8-- (EC-TM-CY) resulted in FcR cell surface expression and phagocytosis, whereas CD8-CD8-, whose TM does not associate with FcR, allowed cell surface expression of (but not phagocytosis by) FcRI. CD8-CD8- also did not allow surface expression of FcRIIIA. Exchanging FcRI and CD8 TMs indicated that the C-terminal 11 amino acids of the FcRI TM are essential for association of FcRI with the chain and phagocytosis. The data indicate that specific sequences in the FcRIIIA and FcRI TMs govern their different interactions with the chain in cell surface expression and phagocytosis and that chain TM sequences are not required for chain–mediated phagocytosis. The data identify a specific region of the FcRI TM and its asparagine as important for FcRI cell surface expression in the absence of the chain and for distinguishing the FcRI and FcRIIIA phenotypes. |
Introduction |
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TopAbstractIntroductionMaterials and methodsResultsDiscussionReferences |
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receptors are important in several cell functions, including endocytosis, phagocytosis, and the release of inflammatory mediators. There are 3 classes of human Fc receptors: FcRI, FcRII, and FcRIII (for reviews, see references 1, 2, 3, 4, 5, 6). The cytoplasmic domains (CY) of FcRIIIA (
chain) and FcRI ( chain) contain no known signaling motifs. However, FcRIIIA and FcRI are associated with a chain7,8, 9, 10, 11 that contains an immunoreceptor tyrosine-based activation motif (ITAM sequence) through which signal transduction can proceed.
The FcRIIIA and FcRI chains interact with the chain through sequences within their homologous transmembrane (TM) regions.12, 13, 14 The chain plays a dual role in FcRIIIA and FcRI signaling. In addition to providing ITAM tyrosines for initiation of the Fc receptor signaling cascades, association with the chain protects the chain of these Fc receptors from degradation in the endoplasmic reticulum, thus facilitating their cell surface expression in monocytes/macrophages.15, 16, 17 Coexpression of the chain also is required for cell surface expression of FcRIIIA in transfected epithelial cells.9, 10 Although signaling by FcRI has been observed to be dependent upon the ITAM of an associated chain, cell surface expression of FcRI in transfected COS-1 cells occurs in the absence of the chain.11 The difference in the requirement of the chain for cell surface expression of FcRIIIA and FcRI provides an approach to further investigate the interaction between the chain and these Fc receptors. To this end, we have constructed chimeric receptors and receptor TM domain mutants in order to (1) examine the interaction of the chain with FcRIIIA and FcRI, and (2) identify TM sequences that contribute to the differences in the FcRIIIA and FcRI phenotypes.
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Materials and methods |
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TopAbstractIntroductionMaterials and methodsResultsDiscussionReferences |
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The exchange and substitution mutants of FcRIIIA, FcRI, CD8, and the human subunit of FcRIIIA and FcRI were constructed by 2-step overlap extension polymerase chain reaction. The mutants and chimeric receptors as well as wild-type (WT) receptors were cloned into the HindIII and XbaI cloning sites of the eucaryotic expression vector pCDNA 3.1/Myc-His B (Invitrogen, San Diego, CA).
Cell culture and transfection of COS-1 cells
COS-1 cells were maintained in high-glucose Dulbecco modified Eagle medium (DMEM; Gibco BRL, Grand Island, NY) containing glutamine (2 mM), streptomycin (100 U/mL), penicillin (100 µg/mL), and 10% heat-inactivated fetal calf serum at 37°C with 5% CO2/95% air. Transient transfections with cDNA were carried out by a modified diethylamino ethyl (DEAE)–Dextran method. Briefly, 5 x 105 COS-1 cells were seeded onto 35-mm well plates 24 hours prior to transfection. Plates were washed twice and incubated for 30 minutes with DMEM (GIBCO BRL, Grand Island, NY) without serum before transfection. Following addition of transfection buffer (1 mL) containing 4 µg plasmid DNA (0.5 µg/mL) and incubation for 4 hours at 37°C, cells were treated with 10% dimethyl sulfoxide in phosphate-buffered saline (PBS) for 1 1/2 minutes and washed twice with DMEM. Cells were studied 48 hours after transfection.
Flow cytometry
Cell surface expression of FcR protein 48 hours after transfection was determined by flow cytometry using anti-FcRIIIA (3G8) or anti-FcRI (32.2) mAbs as the primary antibodies and fluorescein isothiocyanate (FITC)–labeled F(ab)'2 goat anti–mouse IgG antibody (TAGO, Burlingame, CA) as the cross-linking secondary antibody.10, 11 Anti-CD8 mAb was obtained from PharMingen (San Diego, CA).
Phagocytosis of IgG-sensitized RBCs
IgG-coated sheep erythrocytes (EA) were prepared as previously described.10, 11 COS-1 cell transfectants were incubated with washed EA at 37°C for 30 minutes. Unbound EA were removed by extensive washing and stained with Wright-Giemsa to determine the number of cells with bound EA. For assessment of phagocytosis, hypotonic PBS was applied briefly (30 seconds) to remove surface-bound EA. Phagocytosed cells were stained with Wright-Giemsa, and ingested erythrocytes were counted by light microscopy (x 1000). Results were presented as phagocytic index (PI), the number of ingested erythrocytes per 100 COS-1 cells. In indicated experiments, the phagocytic index was corrected for variations in cell surface receptor expression (mean fluorescence intensity, MFI) as determined by flow cytometry.
Western blotting
COS-1 cell transfectants were lysed on plates with NP-40 buffer (1% NP-40, 1% sodium deoxycholate, 0.1% sodium dodecyl sulfate [SDS], 158 mM NaCl, 10 mM Tris [tris(hydroxymethyl)aminomethane], pH 7.2, 5 mM NaEDTA (sodium ethylenediaminetetraacetic acid), 1 mM phenylmethylsulphonyl fluoride, 1 mM Na3VO4) at 4°C for 30 minutes. Myc-tagged Fc receptors and coimmunoprecipitating proteins were immunoprecipitated from cell lysates with anti-Myc antibody (Santa Cruz Biotechnology, Santa Cruz, CA), and proteins were resolved on 15% SDS polyacrylamide. Following electrophoretic transfer to nitrocellulose, proteins were immuno-blotted with anti-His antibody (R&D Systems, Minneapolis, MN) to identify the His-tagged chain. Blots were developed with horseradish peroxidase–conjugated goat antimouse (Bio-Rad, Richmond, CA) and specific bands were detected by enhanced chemiluminescence (ECL, Amersham, Arlington Heights, IL).
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Results |
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TopAbstractIntroductionMaterials and methodsResultsDiscussionReferences |
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RIIIA are detected on the surface of transiently transfected COS-1 cells in the absence of chain expression.9,10 In contrast, cell surface expression of FcRI is evident both in the absence and presence of the chain (references 1, 11, 18, and 19; Table 1). FcRI- and FcRIIIA-mediated phagocytosis also depend on coexpression of the chain.9,11 The association of FcRI and FcRIIIA with the chain occurs through interaction of the individual receptor transmembrane (TM) domains.12, 13, 14 To determine which sequences in the TM regions of FcRI and FcRIIA are required for cell surface expression and phagocytosis, we first used single chain chimeras in which the extracellular domains (EC) and TM regions of these receptors were exchanged (Figure 1).
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The feasibility of using Fc receptor/ chain chimeric receptors for functional studies was based on our observation that appending the chain CY and TM to the EC of FcRIIIA or FcRI produced chimeric receptors RIIIA-- and RI--, EC-TM-CY, which are well expressed in COS-1 cell transfectants.1,19 These chimeric receptors are also functional, as evidenced by their ability to phagocytose EAs with efficiencies comparable to cotransfectants of FcRI or FcRIIIA with the chain (Indik et al1,19; and Table 2).
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Fc receptor chimeras containing the TM of FcRI (RIIIA-RI- and RI-RI-, Figure 1) were also expressed efficiently in transfected COS-1 cells (Table 3). In contrast, the Fc receptor chimera RIIIA-RIIIA- was essentially undetectable on the surface of transfected COS-1 cells (Table 3). Cell surface expression of RI-RIIIA-, which also contains the TM of FcRIIIA, was dramatically reduced compared to that of RI-RI- (Table 3). As expected, phagocytosis mediated by the chimeric FcRs reflect their cell surface expression; that is, chimeras containing the FcRI TM allow surface expression and induce the phagocytosis of EA, whereas those containing the FcRIIIA TM are not expressed (Table 4). We are aware that construction of chimeras may bring the risk of artificial processing of the protein in cellular systems. We therefore also examined expression of other FcRIIIA and FcRI TM chimeras to determine whether profound depression of FcR expression is specific for the TM of FcRIIIA or a function of chimera construction (Table 3).
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Expression of the FcRI EC was consistently most depressed by the FcRIIIA TM (Table 3). The expression of RI-- was 72% ± 25% compared with RI-RI-; the expression of RI-RIIA-RIIA was 87% of RI-RI- (not shown), but the expression of RI-RIIIA- was 14% of RI-RI-. Further, the cell surface expression of the chimera RI-CD8- was similar to that of WT FcRI (Table 3). In contrast, the cell surface expression of RI-RIIIA- was only 11% of WT FcRI. We also observed that the cell surface expression of RIIIA-- was 91% ± 8% of RIIIA-RI-, while expression of RIIIA-RIIIA- was only 7% of RIIIA-RI-. Our observation that the cell surface expression of the CD8-RI-RI chimera is 3- to 5-fold greater than that of the CD8-RIIIA-RIIIA chimera (Table 3) is also consistent with the thesis that the TM of FcRIIIA decreases the potential for receptor cell surface expression. These experiments demonstrate that the differences in cell surface expression between FcRI and FcRIIIA reside largely in the sequences of their TM domains.
The data also suggest that the cytoplasmic domain may contribute to Fc receptor surface expression. For example, the cell surface expression of RIIIA-RI- is consistently greater than the cell surface expression of RIIIA-RI-RIIIA (P = .01), and the cell surface expression of RI-RIIIA-RI is consistently greater than the cell surface expression of RI-RIIIA- (P = .005) or RI-RIIIA-RIIIA. These data further indicate that the chain TM is not required for FcRI and FcRIIIA phagocytic signaling. Thus, dimerization of the chain, which occurs through formation of disulfide bridges between the TM Cys7 cysteines of the chains,7 is not a requirement for Fc receptor–mediated phagocytosis.
We used another series of Fc receptor chimeras to further study the role of the TM domain in Fc receptor expression and function and to identify the sequences of the FcRIIIA and FcRI TMs necessary for interaction with the chain. We constructed chimeric Fc receptors containing the EC and/or TM of CD8, (RI-CD8- [EC-TM-CY], RI-CD8-RI, CD8-CD8-, and CD8--, Figure 2). The inability of chimeras bearing the TM of CD8 to associate with the chain is illustrated in Figure 3. In stable transfectants of FcRI or of RI-CD8-RI in the mouse macrophage cell line P388 (which endogenously expresses the chain), the murine chain coimmunoprecipitated with transfected WT human (h) FcRI but not with transfected hRI-CD8-hRI.
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Both RI-CD8-RI and RI-CD8- were expressed efficiently on the surface of COS-1 cell transfectants. RI-CD8-RI, however, did not mediate phagocytosis either in the absence or presence of cotransfected (Figure 4), due to the inability of the CD8 TM to associate with the chain (Figure 3) and the inability of the FcRI CY to mediate phagocytosis in the absence of the chain.9 Thus, although independent of the chain for surface expression, FcRI does not function as a phagocytic receptor under conditions that do not allow chain/FcRI interaction. In contrast, the chimeric receptor RI-CD8- mediated phagocytosis in the absence of cotransfected (Figure 4), demonstrating again that chain transmembrane sequences and dimerization of the chain are not required for phagocytosis mediated by the chain cytoplasmic domain.
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To further study the requirements of FcRIIIA and FcRI interaction with the chain TM domain, we cotransfected FcRI or FcRIIIA with the CD8(EC)/ chimeras CD8-CD8- or CD8-- (Table 5 and Table 6). In addition to their usefulness for examining TM function, an advantage of CD8(EC)/ chimeras is that CD8 expression, as monitored by flow cytometry using antibody directed to the EC of CD8, serves as an indicator of chain expression. As anticipated, FcRI, but not FcRIIIA, is expressed on the surface of COS-1 cells cotransfected with CD8-CD8- (Tables 5 and 6). Since the FcRI TM does not associate with the CD8 TM, cotransfection of FcRI with CD8-CD8- does not support phagocytic signaling (Table 6). In contrast, cotransfection of either FcRI or FcRIIIA with CD8--, which supplies the chain TM necessary for interaction with these Fc receptors, resulted in cell surface expression of and phagocytosis by both FcRI and FcRIIIA (Tables 5 and 6). Similar results were observed in the presence of Syk kinase (not shown).
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To determine which region(s) of the FcRI TM domain is important for FcRI cell surface expression and its interaction with the chain, we constructed FcRI (EC and CY) chimeras whose first 10 (amino-terminal) TM amino acids were replaced by the first 10 amino acids of the CD8 TM (Figure 2). Transfectants of this chimera were expressed efficiently (not shown), and phagocytosis mediated by cotransfectants with the chain, both in the absence and presence of Syk kinase, testifies to a productive interaction of this chimera with the chain (Figure 4). In contrast, replacement of the 11 carboxyterminal amino acids of the FcRI TM by the 14 carboxyterminal amino acids of the CD8 TM produced a chimera that did not mediate phagocytosis in spite of efficient cell surface expression.
The TM domains of FcRIIIA and FcRI share extensive but incomplete sequence homology (Figure 5). For purposes of this study, we next divided the TM domain into 3 regions, P9, P8, and P4 (Table 7). Mutants were constructed in which the TM P8 region of FcRI was substituted for the TM P8 region of FcRIIIA, FcRIIIA(RI/P8), and vice versa, FcRI(RIII/P8) (Table 7). Transfection with FcRIIIA(RI/P8) demonstrated that the TM P8 region of FcRI increases cell surface expression of FcRIIIA in the absence of the chain 4- to 6-fold (Table 7, lines 1 and 3). In the reciprocal experiment, in which FcRI(RIII/P8) was transfected, surface expression decreased to 60%-80% of WT FcRI (Table 7, lines 2 and 5). There was little or no effect on surface expression when the P9 or P4 regions of the TM domains were exchanged (not shown).
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The most striking difference between the TM P8 regions of FcRI and FcRIIIA is the presence of asparagine in FcRI and aspartic acid in FcRIIIA (Table 7; Figure 5). Replacing aspartic acid with asparagine in FcRIIIA (Asp
Asn) dramatically increased surface expression of FcRIIIA (5- to 8-fold, Table 7, lines 1 and 4). In the reciprocal experiment, replacement of the FcRI TM asparagine with aspartic acid (AsnAsp) decreased surface expression of FcRI by about 50% (Table 7, lines 2 and 6). Interestingly, replacement of asparagine in the FcRI TM with glycine increased expression of FcRI (Table 7, line 7).
We also examined whether there were differences in chain sequences required for the productive interaction of FcRI and FcRIIIA with the chain. Previous studies indicated that the association of the chain with some chain–dependent Fc receptors requires cysteine Cys7 and aspartic acid Asp11 of the chain TM.13 FcRIIIA cotransfected with the mutant chain chimera CD8-(Cys7/Asp11)-, in which Cys7 and Asp11 of the chain TM are replaced by glycines (Figure 5), was not expressed on the cell surface (Table 5), consistent with the observation that elimination of chain/FcRIIIA interaction eliminates surface expression of FcRIIIA. In contrast, FcRI cotransfected with CD8-(Cys7/Asp11)- not only was expressed on the cell surface but also was able to mediate phagocytosis, albeit at a reduced level (Table 6). These data are a further indication that FcRI and FcRIIIA differ in their requirements for cell surface expression and for functional interaction with the chain.
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Discussion |
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TopAbstractIntroductionMaterials and methodsResultsDiscussionReferences |
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RI and FcRIIIA with the chain allows these Fc receptors, which lack cytoplasmic domain tyrosines crucial for the initiation of signaling cascades, to transmit signals from external stimuli to intracellular molecules. Interaction with the chain also plays a role in facilitating cell surface expression of some Fc receptors.9,13,16,17 Cell surface expression of FcRIIIA is not observed in cells obtained from chain knockout mice,16 but expression of FcRI, while greatly diminished, is detectable in a subset of monocytes/macrophages from chain knockout mice (van Vugt et al17 and P. M. Hogarth, oral communication, August 2002).
Differences in FcRI and FcRIIIA cell surface expression in the absence of the chain are more evident in transfectants of COS-1 cells. Only trace amounts of FcRIIIA reach the cell surface of FcRIIIA-transfected COS-1 cells in the absence of chain expression,9,10 while FcRI is efficiently expressed in COS-1 cell transfectants in the absence or presence of the chain (Table 1). We and others have demonstrated that association of the chain with FcRI and FcRIIIA occurs through interactions between the individual transmembrane domains.11,12,14 The TM of FcRI consists of 21 amino acids, 7 identical to those of the FcRIIIA TM (Figure 5). One goal of our studies was to identify FcRI and FcRIIIA TM sequences that contribute to the differences in cell surface expression of these receptors.
Substitution of the FcRI TM P8 region for that of FcRIIIA dramatically increases cell surface expression of FcRIIIA in the absence of the chain. More particularly, substitution of the FcRI P8 asparagine for the FcRIIIA P8 aspartic acid allows a high level of cell surface expression by FcRIIIA in the absence of the chain (Table 7). In the reciprocal experiment, in which aspartic acid is substituted for asparagine in the FcRI TM, FcRI cell surface expression in the absence of the chain was reduced. Our data are consistent with the thesis that negatively charged residues in the TM are determinants for retention and rapid breakdown of some proteins in the endoplasmic reticulum20 and identify the FcRI TM asparagine as important for chain–independent cell surface expression by these Fc receptors.
Expression of FcRI was determined with mAb 32.2 and expression of FcRIIIA with mAb 3G8. Therefore, direct comparison of FcRI and FcRIIIA expression by flow cytometry is not appropriate. We noted, however, that mutating asparagine to aspartic acid does not produce as profound a change in FcRI expression as that induced in FcRIIIA expression by mutating aspartic acid to asparagine in the FcRIIIA TM. In mutating asparagine to aspartic acid, we observed a 2-fold decrease in chain–independent FcRI expression; in mutating aspartic acid to asparagine, we observed a 6- to 8-fold increase in chain–independent FcRIIIA expression (Table 7). One possibility is that the protein degradation apparatus in the endoplasmic reticulum does not interact efficiently with the FcRI TM, even in the presence of a charged amino acid residue in the P8 region. Alternatively, the P4 and/or P9 regions of FcRI may also contribute somewhat in resisting Fc receptor degradation.
We also noted that there is increased -chain independent FcRI expression when the P8 asparagine is changed to glycine (Table 7, line 7). FcRI expression thus appears to increase as the critical P8 residue changes from aspartic acid (negative charge) to asparagine (polar) to glycine. The increase in surface expression of the FcRI glycine mutant may be due to the lack of charge of the substituted amino acid or to its size, each capable of resisting interaction with the protein degradation machinery.
Another goal was to further identify the FcR TM amino acids important for productive interaction of FcRI and FcRIIIA with the chain. Previous studies suggested that charged residues in TM domains are important for protein-protein interaction in the cell membrane.12,13,20, 21, 22 Fc
RI, like FcRIIIA, requires the chain for both surface expression and function in transfected cells.13 The TM of FcRI, which is highly homologous to the TM of FcRIIIA, includes an aspartic acid at the TM position homologous to the aspartic acid in the FcRIIIA TM (Figure 5). Mutation of aspartic acid to alanine in the TM of rat FcRI interfered with chain/FcRI interaction and reduced expression of FcRI,13 and cotransfection with the WT chain, which contains a TM aspartic acid, provided optimal expression levels of FcRIIIA.13 Further, the TM of the 
chain of the T-cell antigen receptor, which is highly homologous to the chain, requires the aspartic acid of the transmembrane domain for optimal association with FcRIIIA.12,21 Our studies of Fc receptor expression and function in the presence of the chain demonstrate that the FcRI TM region containing asparagine is required for productive interaction of FcRI with the chain (Figure 4) and are consistent with a role for polar residues in protein-protein associations in cell membranes.
The chain also interacts with the receptor for IgA.23, 24, 25, 26 Cell surface expression of FcRI is independent of chain association in stable transfectants of a B-cell line, although signaling functions depend upon association with the chain.24 Association between FcRI and is also dependent upon charged residues located within the TM of both FcRI and the chain.24 The 19 amino acid TM region of FcRI displays no obvious homology to FcRI but does contain a positively charged TM residue (arginine 209, Figure 5), which is required for its interaction with the chain.24 Also of note, in FcRI/ chain cotransfectants, chain protein survives in transfectants coexpressing wild-type FcRI (which possesses TM arginine) but does not survive in cells cotransfected with FcRI mutants, which possess a negatively charged TM residue.
Taken together, these studies further identify parameters for Fc receptor cell surface expression and FcRI/FcRIIIA chain association. Our studies confirm the requirement for specific charged or polar TM residues for association of the chain with Fc receptors using the ITAM sequence of the chain for signal transduction. The aspartic acid residue in the TMs of FcRIIIA and FcRI fulfills this function as does the FcRI TM polar residue asparagine. These amino acids also determine the phenotype of chain dependence for Fc receptor cell surface expression. We have now demonstrated that asparagine at this specific TM site allows chain–independent cell surface expression of FcRI and FcRIIIA, while the negatively charged TM residue aspartic acid plays a negative role in survival of unchaperoned Fc receptor molecules traversing the endoplasmic reticulum in transfected cell lines. Having also observed that replacement of asparagine with glycine in the FcRI TM further increases the efficiency of FcRI cell surface expression (Table 7), we suggest that the ability of Fc receptors to survive the action of proteolytic enzymes in the endoplasmic reticulum is related to the charge or polarity of specific TM residues.
In addition, our data indicating that cysteine Cys7 and aspartic acid Asp11 of the chain are essential for the cell surface expression of FcRIIIA but not essential for the cell surface expression of FcRI (Figure 5; Tables 5 and 6) are a further indication that FcRI and FcRIIIA differ in their requirements for cell surface expression and for functional interaction with the chain. Furthermore, since both FcRIIIA and FcRI are associated with chain dimers in vivo7,8 and signaling by these Fc receptors via the chain has been viewed to be contingent upon both chain dimerization and this specific association, our studies also indicate that neither dimerization of an associated chain nor the chain TM region itself is required for Fc receptor–mediated phagocytosis.
In summary, using FcRI and FcRIIIA, which display different phenotypes for surface expression in transfected cells, we have identified a specific region, the C-terminal region, of the FcRI TM and its asparagine as important for FcRI cell surface expression in the absence of the chain. Our data also demonstrate that a chain dimer induced by the chain TM is not required for efficient phagocytosis. These studies further define differences in phagocytic signaling between FcRI and FcRIIIA and extend our understanding of how transmembrane domain sequences influence the function of Fc receptors.
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Footnotes |
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Supported by National Institutes of Health grants AI-22193 and HL-69498.
The publication costs of this article were defrayed in part by page charge payment. Therefore, and solely to indicate this fact, this article is hereby marked "advertisement" in accordance with 18 U.S.C. section 1734.
Reprints: Alan D. Schreiber, Division of Hematology/Oncology, Department of Medicine, BRBII/III, Rm 705, 421 Curie Blvd, University of Pennsylvania School of Medicine, Philadelphia, PA 19104; e-mail: schreibr{at}mail.med.upenn.edu.
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References |
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TopAbstractIntroductionMaterials and methodsResultsDiscussionReferences |
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receptor-mediated phagocytosis. Blood. 1995;86: 4389-4399.RIIA: effect on receptor tyrosine phosphorylation and phagocytosis. Blood. 1994;84: 1753-1759.RII induces tyrosine phosphorylation of multiple proteins including FcRII. J Biol Chem. 1992;267: 5467-5473.RI and FcRIII). J Immunol. 1991;265: 2652-2656.RIIIA transmits a phagocytic signal that requires the cytoplasmic domain of its subunit. J Clin Invest. 1993;92: 1967-1973.[Medline]
[Order article via Infotrieve] subunit are required for a phagocytic signal mediated by FcRIIIA. J Clin Invest. 1992;92: 2073-2079. receptor (CD64) induces phagocytosis in the absence of its cytoplasmic domain: the subunit of FcRIIIA imparts phagocytic function to FcRI. Exper Hematol. 1994;22: 599-606.[Medline]
[Order article via Infotrieve]RIII (CD16) membrane expression and association with CD3 and FcRI- by site directed mutation. J Immunol. 1991;146: 1571-1576.[Abstract] chain deletion results in pleiotrophic effector cell defects. Cell. 1994;76: 519-529.[CrossRef][Medline]
[Order article via Infotrieve] chain is essential for both surface expression and function of human FcRI (CD64) in vivo. Blood. 1996;87: 3593-3599.RII, in the absence of other Fc receptors, mediates a phagocytic signal. J Clin Invest. 1991;88: 1766-1771.[Medline]
[Order article via Infotrieve] chain. Cell. 1992;68: 889-897.[CrossRef][Medline]
[Order article via Infotrieve]R) with FcRI 2 subunits in U937 cells. J Immunol. 1994;153: 3228-3236.[Abstract] chain. J Biol Chem. 1995;270: 29781-29787. association and protects against degradation of bound ligand. J Biol Chem. 1999;274: 7216-7225.RI, CD89) function in transgenic mice requires both FcR chain and CR3 (CD11b/CD18). Blood. 1999;93: 4387-4394.
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| Copyright © 2003 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||
receptor transmembrane domains: role in cell surface expression, 
