The role of N-linked glycosylation in determining the surface expression, G protein interaction and effector coupling of the alpha isoform of the human thromboxane A2 receptor
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|Title:||The role of N-linked glycosylation in determining the surface expression, G protein interaction and effector coupling of the alpha isoform of the human thromboxane A2 receptor||Authors:||Kelley-Hickie, Leanne P.
Kinsella, B. Therese
|Permanent link:||http://hdl.handle.net/10197/3145||Date:||2-May-2003||Abstract:||In humans, thromboxane (TX) A2 signals through two TXA2 receptor (TP) isoforms, termed TPalpha and TPbeta, that diverge exclusively within their carboxyl terminal cytoplasmic domains. The amino terminal extracellular region of the TPs contains two highly conserved Asn (N)-linked glycosylation sites at Asn4 and Asn16. Whilst it has been established that impairment of N-glycosylation of TPalpha significantly affects ligand binding/intracellular signalling, previous studies did not ascertain whether N-linked glycosylation was critical for ligand binding per se or whether it was required for the intracellular trafficking and the functional expression of TPalpha on the plasma membrane (PM). In the current study, we investigated the role of N-linked glycosylation in determining the functional expression of TPalpha, by assessment of its ligand binding, G-protein coupling and intracellular signalling properties, correlating it with the level of antigenic TPalpha protein expressed on the PM and/or retained intracellularly. From our data, we conclude that N-glycosylation of either Asn4 or Asn16 is required and sufficient for expression of functionally active TPalpha on the PM while the fully non-glycosylated TPalphaN4,N16-Q4,Q16 is almost completely retained within the endoplasmic reticulum and remains functionally inactive, failing to associate with its coupling G protein Galphaq and, in turn, failing to mediate phospholipase Cbeta activation.||Funding Details:||Health Research Board||Type of material:||Journal Article||Publisher:||Elsevier||Copyright (published version):||2003 Elsevier Science B.V.||Keywords:||Thromboxane receptor;N-linked glycosylation;Surface expression;G protein interaction;Effector signalling||Subject LCSH:||Thromboxanes
|DOI:||10.1016/S0304-4165(03)00059-X||Language:||en||Status of Item:||Peer reviewed|
|Appears in Collections:||Conway Institute Research Collection|
Biomolecular and Biomedical Science Research Collection
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