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

Cross-linking of FCGRIIA with IgG-coated Ag

Stable Identifier

R-HSA-1861621

Type

Reaction [binding]

Species

Homo sapiens

Compartment

plasma membrane

ReviewStatus

5/5

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Cross-linking of FCGRIIA with IgG-coated Ag

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FCGRII (CD32) is a low-affinity receptor encoded by three different genes (A, B and C) (Brooks et al. 1989). FCGRIIA functions as a single-chain transmembrane receptor containing both the ligand-binding extracellular domain and a signal transducing cytoplasmic domain that contains distinct immunoreceptor tyrosine-based activation motif (ITAM). This ITAM-like domain in FCGRIIA contains two YXXL motifs with a spacer sequence of 12 amino acids instead of the usual 7. Isoform FCGRIIB is expressed in various leukocytes, including human monocytes and, as opposed to the activating Fc receptors it has an immunoreceptor tyrosine-based inhibitory motif (ITIM) and negatively regulates phagocytosis (Van den Herik-Oudijk IE et al. 1995, Mitchell et al. 1994, Tridandapani et al. 2002).
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 within the ITAM located on the cytoplasmic portion of FCGRIIA by membrane-associated tyrosine kinases of the Src family (Mitchell et al. 1994).

Literature References

PubMed ID	Title	Journal	Year
7521687	Substitutions and deletions in the cytoplasmic domain of the phagocytic receptor Fc gamma RIIA: effect on receptor tyrosine phosphorylation and phagocytosis Indik, ZK, Huang, MM, Mitchell, MA, Pan, XQ, Chien, P, Schreiber, AD	Blood	1994
7718892	Identification of signaling motifs within human Fc gamma RIIa and Fc gamma RIIb isoforms Van den Herik-Oudijk, IE, Capel, PJ, van der Bruggen, T, van de Winkel, JG	Blood	1995
2529342	Structure and expression of human IgG FcRII(CD32). Functional heterogeneity is encoded by the alternatively spliced products of multiple genes Ravetch, JV, Qiu, WQ, Luster, AD, Brooks, DG	J Exp Med	1989