Disease relevance of FCGR1A

• Thus, Fc gamma RI-positive neutrophils displayed enhanced ADCC activity to glioma (A1207), squamous cell (A431), and ovarian (SK-ov3) carcinoma cell lines [1].
• A correlation was found between the phagocytosis of IgG-sensitized ox erythrocytes or opsonized Escherichia coli and the decreased expression of Fc gamma RI and CR3 [2].
• The receptor (FcRI) may also be involved in CD4-independent infection of human macrophages by human immunodeficiency virus [3].
• Involvement of Fc gamma RI (CD64) in the mechanism of HIV-1 inhibition by polyclonal IgG purified from infected patients in cultured monocyte-derived macrophages [4].
• Differential Enhancement of Dengue Virus Immune Complex Infectivity Mediated by Signaling-Competent and Signaling-Incompetent Human Fc{gamma}RIA (CD64) or Fc{gamma}RIIA (CD32) [5].

High impact information on FCGR1A

• The high affinity receptor that binds the Fc domain of immunoglobulin G (IgG) subclasses 1 and 3 (Fc gamma RI) mediates important immune defense functions by inducing cell surface changes on human leukocytes [6].
• In this article, we document direct high affinity binding of Fc gamma RI to the actin filament cross-linking protein, actin-binding protein (ABP) [6].
• The recognition of these IgG-sensitized red cells in vitro by Fc gamma RI (an Fc gamma-receptor protein that binds monomeric IgG) on blood monocytes from the patients was also significantly decreased (P less than 0.001) but was partially improved by hemodialysis [7].
• Interferon-activated protein complexes bind enhancers present in the promoters of early response genes such as the high-affinity Fc gamma receptor gene (Fc gamma RI) [8].
• Neutralization of interleukin 6, a cytokine present in SFs which is known to activate Stat3, abolished the activation of Stat-SF and inhibited the induction of Fc gamma RI expression by SFs [9].

Chemical compound and disease context of FCGR1A

• Expression patterns of the lipopolysaccharide receptor CD14, and the FCgamma receptors CD16 and CD64 on polymorphonuclear neutrophils: data from patients with severe bacterial infections and lipopolysaccharide-exposed cells [10].
• We conclude that IGFR1 and integrin action are linked in these breast cancer cells as disruption of integrin binding to its receptor influences IGF signaling pathways [11].
• Our data suggest that enhanced synthesis of survivin protein mediated by the IGFR/EGFR heterodimer counteracts the antitumor action of erlotinib, indicating the needs of integration of IGF-IR-targeted agents to the treatment regimens with EGFR TKI for patients with lung cancer [12].
• In SH-SY5Y human neuroblastoma cells, treatment with IGF-I induced concentration- and time-dependent tyrosine phosphorylation of the type I IGF receptor (IGF-IR) and extracellular signal-regulated protein kinases (ERK) 1 and 2 [13].
• This work describes a reciprocal relationship between cell density and levels of insulin-like growth factor receptors (IGFR) in MCF7 human breast cancer cells, which adds a new dimension to the mechanism of cross-talk between estrogen and insulin-like growth factors in the regulation of breast cancer cell growth [14].

Biological context of FCGR1A

• Curiously, the three genes in this recently duplicated gene family flank the centromere of human chromosome 1, with FCGR1B located at 1p12 and both FCGR1A and FCGR1C located at 1q21 [15].
• High resolution mapping of the binding site on human IgG1 for Fc gamma RI, Fc gamma RII, Fc gamma RIII, and FcRn and design of IgG1 variants with improved binding to the Fc gamma R [16].
• By contrast, culture with IL-3 caused an up-regulation of eosinophil FcRII expression but did not induce expression of FcRI or FcRIII [17].
• Coligation of either LIR with Fcgamma receptor I (CD64) inhibits tyrosine phosphorylation of the associated Fc receptor gamma chain and Syk molecules, as well as intracellular calcium mobilization [18].
• The modulation by dexamethasone and interferon-gamma of Fc gamma RI protein expression on U937 cells was markedly different from that of Fc gamma RII in both magnitude and kinetics [19].

Anatomical context of FCGR1A

• We show here that neutrophils strongly express Fc gamma RI after in vivo application of recombinant human granulocyte colony-stimulating factor (rhG-CSF) [20].
• The absence of the high-affinity Fc gamma RI (CD64) suggests that antigenic sensitization of basophils by monomeric IgG does not occur [21].
• Our results demonstrate that calcitriol, alone or in combination with cytokines, modulates Fc alpha R, Fc epsilon RII, Fc gamma RI, and Fc gamma RII expression on human mononuclear phagocytes, as well as Fc gamma R-mediated phagocytosis [22].
• Furthermore, CRP-activated endothelial cells supported monocyte rolling, arrest, and transmigration in shear flow (2 dyn/cm2), and this was also inhibited by preincubation with antibodies to CD32 and CD64 [23].
• The uptake of LDL-IC by human macrophages: predominant involvement of the Fc gamma RI receptor [24].

Associations of FCGR1A with chemical compounds

• Treatment with dexamethasone decreased Fc gamma RI expression by 39%, and also inhibited by 40% the increase induced by interferon-gamma [19].
• In the present report we demonstrate that replacement of contact residues for galactose on the alpha(1-6) arm does not affect Fc gamma RI and Fc gamma RII recognition while replacement of Asp 265, a contact for a 'core' N-acetylglucosamine residue, results in a loss of Fc gamma RI and Fc gamma RII recognition [25].
• Such rapid modulation of the high-affinity Fc gamma RI receptor by integrin cross-linking may reflect the requirement for rapid up-regulation of PMN effector functions, after interaction with endothelial cells, platelets or bacteria [26].
• Macrophages were exposed to green fluorescent 1-micron polystyrene beads before labeling for Fc gamma RI, Fc gamma R-II, and Fc gamma R-III, respectively, with 32.2, 2E1, and 3G8 monoclonal antibodies (MoAbs) and a phycoerythrin (PE)-conjugated secondary Ab to permit dual-channel analysis of fluorescence intensity by FACS [27].
• The results shown here demonstrate a distinct, indirect mechanism of cross-modulation between cytokine and steroid receptor signaling that integrates Stat1 and GR pathways with cell type-specific PU.1 transcription factor in the regulation of Fc gamma RI gene transcription [28].

Physical interactions of FCGR1A

• These results demonstrate both physical and functional association of the Fc gamma RI/Fc epsilon RI gamma receptor complex with hck and lyn, and suggest a potential signal transducing role for these kinases in monocyte/macrophage activation [29].
• SHC was tyrosine phosphorylated in response to Fc gamma RI stimulation of U937IF cells and bound to the SH2 domain of GRB2 in a stimulation-dependent manner [30].
• Histidine-rich glycoprotein binds to DNA and Fc gamma RI and potentiates the ingestion of apoptotic cells by macrophages [31].
• Three types of FcR react with IgG: Fc gamma RI is a high-affinity receptor binding IgG monomers whereas Fc gamma RII and Fc gamma RIII are low-affinity receptors binding IgG immune complexes; the three types of Fc gamma R are members of the Ig superfamily [32].
• A CRP molecule that was mutated in the amino acid sequence homologous to the IgG sequence proposed to interact with Fc gamma RI failed to bind to transfected cells, but retained the ability to bind to the CRP-R on monocytic cells [33].

Enzymatic interactions of FCGR1A

• Thus, Fc gamma RI and Fc gamma RII appear to be functionally coupled to a nonreceptor tyrosine kinase that phosphorylates PLC-gamma 1 after receptor cross-linking, thereby causing activation of PLC-gamma 1 [34].

Regulatory relationships of FCGR1A

• MHC class II Ag, and Fc gamma RI are both upregulated in the presence of IFN-gamma [35].
• The potential of CD33 to function as an inhibitory receptor was demonstrated by its ability to down-regulate CD64-induced calcium mobilization in U937 [36].
• Assays of STAT1 function in M. tuberculosis-treated cells also revealed no defect in activation of a minimal gamma-activated sequence construct or STAT1 recruitment to and binding at the endogenous CD64 promoter [37].
• Selective targeting of human lymphokine-activated killer cells by CD3 monoclonal antibody against the interferon-inducible high-affinity Fc gamma RI receptor (CD64) on autologous acute myeloid leukemic blast cells [38].
• GR activated the natural Fc gamma RI promoter construct, and this response required both Stat1 and the Ets family transcription factor PU [28].

Other interactions of FCGR1A

• Northern analysis of CD64 and p47 phox mRNAs confirmed the findings with the PCR method [39].
• For example, the Fc gamma receptors Fc gamma RI and Fc gamma RIIIA induce signaling largely by association with a gamma subunit containing a conserved cytoplasmic motif (ITAM) whose tyrosines are phosphorylated following receptor stimulation [40].
• Although Fc gamma RIIA utilizes tyrosines within its own cytoplasmic domain for signaling while Fc gamma RI utilizes the cytoplasmic tyrosines of its associated gamma subunit, our results indicate sharing of several proteins for signaling in monocytes by these Fc receptors [41].
• In contrast to U937 cells, TNF-alpha did not enhance significantly Fc gamma RI expression on human monocytes [42].
• FCGR1B was found at 1p12, whereas both FCGR1A and FCGR1C were localized to 1q21 [43].

Analytical, diagnostic and therapeutic context of FCGR1A

• We also determined the changes in the expression of both Fc gamma RI and Fc gamma RII protein following treatment with these agents by flow cytometry [19].
• We have used fluorescence in situ hybridization analysis to localize the Fc gamma RI gene to human chromosome 1 [44].
• The differential affinity of the human FCGR polymorphic alleles for 3F8 may influence the effectiveness of antibody immunotherapy [45].
• We thus first determined by RT-PCR that resting human mast cells exhibit minimal message for Fc gamma RI [46].
• Fc gamma RI expression on PMNs correlated (R = 0.79; p < .001) with plasma concentrations of endogenous or recombinant G-CSF in healthy volunteers and in patients undergoing high-dose chemotherapy and autologous bone marrow transplantation [47].

References