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.

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Neuschäfer-Rube, Frank (författare)

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.

Artikel/kapitelEngelska2004

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2004
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LIBRIS-ID:oai:lup.lub.lu.se:052b0b73-d88d-45b5-8981-e6d6bbe47eb8
https://lup.lub.lu.se/record/121745URI
https://doi.org/10.1042/BJ20031820DOI

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Språk:engelska
Sammanfattning på:engelska

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Ämneskategori:art swepub-publicationtype
Ämneskategori:ref swepub-contenttype

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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analysis of proteolytic phosphopeptides of the wild-type receptor and mutants in which groups of Ser/Thr residues had been replaced by Ala, the principal phosphorylation site was mapped to a Ser/Thr-containing region comprising residues 370–382, the presence of which was necessary and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.

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Biuppslag (personer, institutioner, konferenser, titlar ...)

Hermosilla, Ricardo (författare)
Rehwald, Mathias (författare)
Rönnstrand, LarsLund University,Lunds universitet,Institutionen för translationell medicin,Medicinska fakulteten,Department of Translational Medicine,Faculty of Medicine(Swepub:lu)klke-lro (författare)
Schülein, Ralf (författare)
Wernstedt, Christer (författare)
Püschel, Gerhard (författare)
Institutionen för translationell medicinMedicinska fakulteten (creator_code:org_t)

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Ingår i:Biochemical Journal379:3, s. 573-5850264-6021

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Av författaren/redakt...: Neuschäfer-Rube, ...; Hermosilla, Rica ...; Rehwald, Mathias; Rönnstrand, Lars; Schülein, Ralf; Wernstedt, Chris ...; visa fler...; Püschel, Gerhard; visa färre...

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NATURVETENSKAP: NATURVETENSKAP; och Biologi; och Biokemi och mole ...

Artiklar i publikationen: Biochemical Jour ...

Av lärosätet: Lunds universitet

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