FCGR3A

Case Study 1: Anil K Chauhan, 2017

Recognition of Ab-opsonized pathogens by immune cells triggers both TLR and Fc receptor signaling. Fc receptors endocytose modified nucleic acids bound to Abs and deliver them to endosomes, where they are recognized by nucleic acid-sensing TLRs (NA-TLRs). The researchers show that in CD4+ T cells, NA-TLRs, TLR3, TLR8, and TLR9 are upregulated by FcγRIIIa-pSyk cosignaling and localize with FcγRIIIa on the cell surface. TLR9 accumulates on the cell surface, where it recognizes CpG oligonucleotide 2006. Subcellular location of NA-TLRs is a key determinant in discriminating self versus viral nucleic acid. Hydroxychloroquine used for treating systemic lupus erythematosus and a Syk inhibitor blocked NA-TLR localization with FcγRIIIa. Engaging TLR9 with CpG oligonucleotide contributes to the development of IL17A+ and IL-21+ populations. RNA-sequencing analysis showed upregulation of proinflammatory cytokines, NF-κB signaling, and heat shock protein pathway RNA transcripts. These data suggest a role for FcγRIIIa-pSyk cosignaling in modulating NA-TLR responses in human CD4+ T cells by affecting the amounts and cellular distribution.

Fig1. Flow staining in P116 cells upon FcγRIIIa-pSyk costimulation shows binding of Alexa Fluor 488- CpG ODN 2006 within 10 minutes in TLR9+ (22%) cells.

Fig2. Both MyD88 and HMGB1 moved to the cell surface and localized with FcγRIIIa in cells costimulated by FcγRIIIa-pSyk and not with CD28.

Case Study 2: Per Flodbring Larsson, 2022

Low-affinity immunoglobulin gamma Fc region receptor III-A (FcγRIIIa) is a cell surface protein that belongs to a family of Fc receptors that facilitate the protective function of the immune system against pathogens. However, the role of FcγRIIIa in prostate cancer (PCa) progression remained unknown. PCa patients with an elevated level of FcγRIIIa expression had poorer biochemical recurrence (BCR)-free survival compared with those with lower FcγRIIIa expression, suggesting that FcγRIIIa is of clinical importance in PCa. We demonstrated that overexpression of FcγRIIIa increased the proliferative ability of PCa cell line C4-2 cells, which was accompanied by the upregulation of androgen receptor (AR) and phosphatidylinositol-4-phosphate 5-kinase alpha (PIP5Kα), which are the key players in controlling PCa progression. Conversely, targeted inhibition of FcγRIIIa via siRNA-mediated knockdown or using its inhibitory antibody suppressed growth of xenograft PC-3 and PC-3M prostate tumors and reduced distant metastasis in xenograft mouse models. Similarly, inhibition of PIP5K1α decreased FcγRIIIa expression in PCa cells. FcγRIIIa physically interacted with PIP5K1α and AR via formation of protein-protein complexes, suggesting that FcγRIIIa is functionally associated with AR and PIP5K1α in PCa cells.

Fig3. The effect of FcγRIIIa overexpression on the tumorigenic ability of C4-2 cells was assessed using tumor-spheroid formation assays.

Fig4. The effect of inhibition of AR using enzalutamide on FcγRIIIa expression in LNCaP cells was assessed using immunoblot analysis.

Fig1. Schematic representation of FcγRIIIA activationinducing MDSCs to alter CD4+ T cell subsets by enhancing glycolysis in Sjögren syndrome. (Jingjing Qi, 2023)

Fig2. Graphical hypothesis of NK/NKT cells model in NMOSD. (Shuhei Nishiyama, 2022)

FCGR3A involved in several pathways and played different roles in them. We selected most pathways FCGR3A participated on our site, such as Phagosome, Osteoclast differentiation, Natural killer cell mediated cytotoxicity, which may be useful for your reference. Also, other proteins which involved in the same pathway with FCGR3A were listed below. Creative BioMart supplied nearly all the proteins listed, you can search them on our site.

FCGR3A has several biochemical functions, for example, IgG binding. Some of the functions are cooperated with other proteins, some of the functions could acted by FCGR3A itself. We selected most functions FCGR3A had, and list some proteins which have the same functions with FCGR3A. You can find most of the proteins on our site.

FCGR3A has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with FCGR3A here. Most of them are supplied by our site. Hope this information will be useful for your research of FCGR3A.

drozitumab; FCGR1A; ZBTB25; q81sn0_bacan