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Palmitoylation of platelet‐activating factor receptor is required for its lipid raft targeting and signaling
Author(s) -
Lu Jing,
Caplan Michael S,
Jilling Tamas
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.1007.11
Subject(s) - palmitoylation , occludin , lipid raft , microbiology and biotechnology , chemistry , polyunsaturated fatty acid , arachidonic acid , docosahexaenoic acid , biochemistry , receptor , biology , fatty acid , tight junction , cysteine , enzyme
Platelet‐activating factor receptor (PAFR) signaling has been implicated in a broad range of pathologies. Site‐directed mutagenesis, recombinant protein analysis, sucrose density fractionation and radiolabeling studies indicate that the PAFR is targeted to lipid rafts and can be palmitoylated on cysteine 317. Polyunsaturated fatty acids (PUFA) block PAF‐induced apoptosis, ion transport and proinflammatory gene expression. Palmitate incorporation into the PAFR is inhibited in the presence of excess arachidonic acid (AA), docosahexaenoic acid (DHA), and a palmitoylation inhibitor 2‐bromopalmitate (2‐BP). PAFR solubilized from membranes of untreated HT29‐CL19A colonocytes sediments to the 30% sucrose density fraction similar to occludin, a bone fide lipid raft marker in these cells. Both the PAFR and occludin are displaced from this fraction and they are detected in the lighter 15% to 30% interface (both PAFR and occludin) and in the 15% sucrose fraction (occludin) when solubilized from mebranes derived from HT29‐CL19A cells treated with 2‐BP AA or DHA. These data are consistent with the notion that, in addition to their well known effects on prostaglandin biosytnthesis, PUFA can act via a novel mechanism by which they alter posttranslational modification and they displace PAFR from lipid rafts. Supported by NIH DK062960.