Raft localisation of FcγRIIa and efficient signaling are dependent on palmitoylation of cysteine 208

Ligand-dependent aggregation of Fc gamma RIIa initiates multiple biochemical processes including the translocation to detergent resistant membrane domains (DRMs) and receptor tyrosine phosphorylation. Palmitoylation of cysteine residues is considered to be one process that assists in the localisation of proteins to DRMs. Within the juxtamembrane region of Fc gamma RIIa there is cysteine residue (C208) that we show to be palmitoylated. Mutation of this cysteine residue results in the disruption of Fc gamma RIIa translocation to DRMs as empirically defined by insolubility at high Triton X-100 concentrations. This study also demonstrates that the lack of lipid raft association diminishes Fc gamma RIIa signaling as measured by receptor phosphorylation and calcium mobilisation functions suggesting that Fc gamma RIIa signaling is partially dependent on lipid rafts. (C) 2005 Elsevier B.V. All rights reserved.