The unique cytoplasmic domain of human FcγRIIIA regulates receptor-mediated function.

Ligand specificity characterizes receptors for Abs and many other immune receptors, but the common use of the FcR γ-chain as their signaling subunit challenges the concept that these receptors are functionally distinct. We hypothesized that elements for specificity might be determined by the unique cytoplasmic domain (CY) sequences of the ligand-binding α-chains of γ-chain-associated receptors. Among Fcγ receptors, a protein kinase C (PKC) phosphorylation consensus motif [RSSTR], identified within the FcγRIIIa (CD16A) CY by in silico analysis, is specifically phosphorylated by PKCs, unlike other FcRs.

Serine phosphorylation of FcγRI cytoplasmic domain directs lipid raft localization and interaction with protein 4.1G.

The high-affinity IgG receptor (CD64, FcγRI) has several special capacities, including the receptor-stimulated cleavage of the cell surface B cell-activating factor of the TNF superfamily (TNFSF13B). With the use of the yeast two-hybrid system, we and others have shown that FcγRI interacts with protein 4.1G (EPB41L2).