Search: WFRF:(Wernstedt Christer)
> (2000-2004) >
Identification of a...
Identification of a Ser/Thr cluster in the C-terminal domain of the human prostaglandin EP4-R essential for agonist-induced beta-arrestin1 recruitment that differs from the apparent principal phosphorylation site.
-
Neuschäfer-Rube, Frank (author)
-
Hermosilla, Ricardo (author)
-
Rehwald, Mathias (author)
-
show more...
-
- Rönnstrand, Lars (author)
- Lund University,Lunds universitet,Institutionen för translationell medicin,Medicinska fakulteten,Department of Translational Medicine,Faculty of Medicine
-
Schülein, Ralf (author)
-
Wernstedt, Christer (author)
-
Püschel, Gerhard (author)
-
show less...
-
(creator_code:org_t)
- 2004
- 2004
- English.
-
In: Biochemical Journal. - 0264-6021. ; 379:3, s. 573-585
- Related links:
-
https://portal.resea... (primary) (free)
-
show more...
-
http://dx.doi.org/10...
-
https://lup.lub.lu.s...
-
https://doi.org/10.1...
-
show less...
Abstract
Subject headings
Close
- hEP4-R (human prostaglandin E2 receptor, subtype EP4) is a Gs-linked heterotrimeric GPCR (G-protein-coupled receptor). It undergoes agonist-induced desensitization and internalization that depend on the presence of its C-terminal domain. Desensitization and internalization of GPCRs are often linked to agonist-induced b-arrestin complex formation, which is stabilized by phosphorylation. Subsequently b-arrestin uncouples the receptor from its G-protein and links it to the endocytotic machinery. The C-terminal domain of hEP4-R contains 38 Ser/Thr residues that represent potential phosphorylation sites. The present study aimed to analyse the relevance of these Ser/Thr residues for agonist-induced phosphorylation, interaction with b-arrestin and internalization. In response to agonist treatment, hEP4-R was phosphorylated. By analysis of proteolytic phosphopeptides of the wild-type receptor and mutants in which groups of Ser/Thr residues had been replaced by Ala, the principal phosphorylation site was mapped to a Ser/Thr-containing region comprising residues 370–382, the presence of which was necessary and sufficient to obtain full agonist-induced phosphorylation. A cluster of Ser/Thr residues (Ser-389–Ser-390–Thr-391–Ser-392) distal to this site, but not the principal phosphorylation site, was essential to allow agonist-induced recruitment of b-arrestin1. However, phosphorylation greatly enhanced the stability of the b-arrestin1–receptor complexes. For maximal agonist-induced internalization, phosphorylation of the principal phosphorylation site was not required, but both b-arrestin1 recruitment and the presence of Ser/Thr residues in the distal half of the C-terminal domain were necessary.
Subject headings
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
Publication and Content Type
- art (subject category)
- ref (subject category)
Find in a library
To the university's database