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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
Date Issued
2003-05-02
Date Available
2011-09-01T15:11:06Z
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.
Sponsorship
Health Research Board
Other Sponsorship
Wellcome Trust
Enterprise Ireland
Type of Material
Journal Article
Publisher
Elsevier
Journal
Biochimica et Biophysica Acta (BBA) - General Subjects
Volume
1621
Issue
2
Start Page
193
End Page
203
Copyright (Published Version)
2003 Elsevier Science B.V.
Subject – LCSH
Thromboxanes
Glycosylation
Protein-protein interactions
Web versions
Language
English
Status of Item
Peer reviewed
ISSN
0304-4165
This item is made available under a Creative Commons License
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