Reactome | Cross-linking of FCGRIA with IgG-coated Ag

Cross-linking of FCGRIA with IgG-coated Ag

Stable Identifier

R-HSA-2029455

Type

Reaction [binding]

Species

Homo sapiens

Compartment

plasma membrane, extracellular region

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Cross-linking of FCGRIA with IgG-coated Ag

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FCGRI is coded by three different genes (A, B, and C) and is expressed on most myeloid cells including monocytes, macrophages and dendritic cells (Allen & Seed 1988). FCGRI is a high affinity IgG receptor capable of binding monomeric IgG. FCGRI exists as a complex containing ligand (IgG) binding extracellular alpha-chain and homodimer of signal transducing FcR gamma (CD3G) chains, or a heterodimer of signal transducing FcR gamma and zeta chains (Ernst et al. 1993, Scholl & Geha 1993, van Vugt et al. 1996). The cytoplasmic domain of FCGRI does not have signaling motifs, however it is suggested that the gamma-subunit might be required for generating the phagocytic signal (Duchemin et al. 1994, Indik et al. 1995).
The first step in Fc-gamma receptor (FCGR) phagocytosis is binding and clustering of FCGRs by IgG-coated foreign particles. FCGR are clustered at the cell surface by multivalent antigen-antibody complexes and recruited to lipid raft micro domains; monovalent ligand binding is insufficient to generate a signal. This cross-linking results in the localization of FCGRs into lipid rafts and this may aid in recruiting and complexing with additional signalling proteins associated with lipid rafts (Bournazos et al. 2009, Kwiatkowska & Sobota 2001, Kono et al. 2002). This is followed by phosphorylation of the tyrosine residues with in the immuno tyrosine activation motif (ITAM) located on the cytoplasmic portion of accessory gamma/zeta chains by membrane-associated tyrosine kinases of the Src family (Duchemin et al. 1994, van Vugt et al. 1996).

Literature References

PubMed ID	Title	Journal	Year
7512959	Clustering of the high affinity Fc receptor for immunoglobulin G (Fc gamma RI) results in phosphorylation of its associated gamma-chain Duchemin, AM, Ernst, LK, Anderson, CL	J Biol Chem	1994
8327478	Association of the high-affinity receptor for IgG (Fc gamma RI) with the gamma subunit of the IgE receptor Ernst, LK, Duchemin, AM, Anderson, CL	Proc Natl Acad Sci U S A	1993
7516890	The high affinity Fc gamma receptor (CD64) induces phagocytosis in the absence of its cytoplasmic domain: the gamma subunit of Fc gamma RIIIA imparts phagocytic function to Fc gamma RI Indik, ZK, Hunter, S, Huang, MM, Pan, XQ, Chien, P, Kelly, C, Levinson, AI, Kimberly, RP, Schreiber, AD	Exp Hematol	1994
8611682	FcR gamma-chain is essential for both surface expression and function of human Fc gamma RI (CD64) in vivo van Vugt, MJ, Heijnen, AF, Capel, PJ, Park, SY, Ra, C, Saito, T, Verbeek, JS, van de Winkel, JG	Blood	1996
8541526	The molecular dissection of Fc gamma receptor mediated phagocytosis Indik, ZK, Park, JG, Hunter, S, Schreiber, AD	Blood	1995