β-arrestin1 phosphorylation by GRK5 regulates G protein-independent 5-HT4 receptor signalling

被引：54

作者：

Barthet, Gael ^{[1
,2
]}

Carrat, Gaelle ^{[1
,2
]}

Cassier, Elizabeth ^{[1
,2
]}

Barker, Breann ^{[3
]}

Gaven, Florence ^{[1
,2
]}

Pillot, Marion ^{[1
,2
]}

Framery, Berenice ^{[1
,2
]}

Pellissier, Lucie P. ^{[1
,2
]}

Augier, Julie ^{[1
,2
]}

Kang, Dong Soo ^{[3
]}

Claeysen, Sylvie ^{[1
,2
]}

Reiter, Eric ^{[4
,5
,6
]}

Baneres, Jean-Louis ^{[7
]}

Benovic, Jeffrey L. ^{[3
]}

Marin, Philippe ^{[1
,2
]}

Bockaert, Joel ^{[1
,2
]}

Dumuis, Aline ^{[1
,2
]}

机构：

[1] Univ Montpellier, CNRS, Inst Genom Fonct, F-34094 Montpellier 5, France

[2] INSERM, Montpellier, France

[3] Thomas Jefferson Univ, Dept Biochem & Mol Biol, Philadelphia, PA 19107 USA

[4] INRA, Physiol Reprod & Comportements GMR6175, F-37380 Nouzilly, France

[5] CNRS, Nouzilly, France

[6] Univ Tours, Nouzilly, France

[7] CNRS, Inst Biomol Max Mousseron, UMR5247, Montpellier, France

来源：

EMBO JOURNAL | 2009年 / 28卷 / 18期

关键词：

ERK signalling; GRK5; p-S-412-beta-arrestin1; Src family kinase; 5-HT4R; BETA-ADRENERGIC-RECEPTOR; COUPLED-RECEPTOR; PARTIAL AGONIST; ERK ACTIVATION; ARRESTIN; KINASES; SRC; DESENSITIZATION; ENDOCYTOSIS; EXPRESSION;

D O I：

10.1038/emboj.2009.215

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

G protein-coupled receptors (GPCRs) have been found to trigger G protein-independent signalling. However, the regulation of G protein-independent pathways, especially their desensitization, is poorly characterized. Here, we show that the G protein-independent 5-HT4 receptor (5-HT4R)-operated Src/ERK (extracellular signal-regulated kinase) pathway, but not the G(s) pathway, is inhibited by GPCR kinase 5 (GRK5), physically associated with the proximal region of receptor' C-terminus in both human embryonic kidney (HEK)-293 cells and colliculi neurons. This inhibition required two sequences of events: the association of beta-arrestin1 to a phosphorylated serine/threonine cluster located within the receptor C-t domain and the phosphorylation, by GRK5, of beta-arrestin1 (at Ser(412)) bound to the receptor. Phosphorylated beta-arrestin1 in turn prevented activation of Src constitutively bound to 5-HT(4)Rs, a necessary step in receptor-stimulated ERK signalling. This is the first demonstration that beta-arrestin1 phosphorylation by GRK5 regulates G protein-independent signalling. The EMBO Journal (2009) 28, 2706-2718. doi: 10.1038/emboj.2009.215; Published online 6 August 2009

引用

页码：2706 / 2718

页数：13

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