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Palmitoylation of the TPβ isoform of the human thromboxane A 2 receptor: Implications for receptor trafficking
Author(s) -
Kinsella B. Therese,
Reid Helen M.
Publication year - 2008
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.22.1_supplement.725.4
Subject(s) - internalization , palmitoylation , agonist , chemistry , g protein coupled receptor , receptor , gene isoform , gtpgammas , microbiology and biotechnology , biochemistry , biology , cysteine , enzyme , gene
Palmitoylation is a prevalent feature of G protein coupled receptors (GPCRs). We investigated whether the TPα and TPβ isoforms of the human thromboxane (TX)A 2 receptor are palmitoylated and the functional consequences thereof. Consistent with three cysteines within its unique C‐tail, TPβ, but not TPα, is palmitoylated at Cys 347 and, to a lesser extent, at Cys 373,377 . Whilst impairment of palmitoylation did not affect ligand affinity, [Ca 2+ ] i mobilization by TPβ C347S , but not TPβ C373S or TPβ C373,377S was significantly reduced relative to TPβ WT suggesting that palmitoylation at Cys 347 is required for Gq/phospholipase Cβ coupling. As TPβ, but not TPα, undergoes agonist‐induced and tonic‐ internalization, we investigated whether palmitoylation affects TPβ internalization. It was found that agonist‐ and tonic‐internalization by TPβ C373S , TPβ C373,377S and TPβ C347,373,377S was significantly reduced compared to TPβ WT . Whilst TPβ C347S underwent reduced agonist‐ internalization, it underwent tonic‐ internalization to a similar extent as TPβ. The deficiency in agonist‐induced internalization by TPβ C347S was overcome by over‐expression of β‐arrestins. Collectively, data herein suggest that whilst palmitoylation of TPβ at Cys 373,377 is critical for agonist‐ and tonic‐ internalization, palmitoylation at Cys 347 may determine which pathway is followed. * This work was supported by The Wellcome Trust .