|[beta]|-arrestin1 phosphorylation by GRK5 regulates G protein-independent 5-HT4 receptor signalling Export

@article{citeulike:5391421, abstract = {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 Gs 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 –arrestin1 to a phosphorylated serine/threonine cluster located within the receptor C-t domain and the phosphorylation, by GRK5, of –arrestin1 (at Ser412) bound to the receptor. Phosphorylated -arrestin1 in turn prevented activation of Src constitutively bound to 5-HT4Rs, a necessary step in receptor-stimulated ERK signalling. This is the first demonstration that -arrestin1 phosphorylation by GRK5 regulates G protein-independent signalling.}, author = {Barthet, Gael and Carrat, Gaelle and Cassier, Elizabeth and Barker, Breann and Gaven, Florence and Pillot, Marion and Framery, Berenice and Pellissier, Lucie P. and Augier, Julie and Kang, Dong S. and Claeysen, Sylvie and Reiter, Eric and Baneres, Jean-Louis and Benovic, Jeffrey L. and Marin, Philippe and Bockaert, Joel and Dumuis, Aline}, citeulike-article-id = {5391421}, citeulike-linkout-0 = {http://dx.doi.org/10.1038/emboj.2009.215}, citeulike-linkout-1 = {http://dx.doi.org/10.1038/emboj2009215a}, day = {06}, doi = {10.1038/emboj.2009.215}, issn = {0261-4189}, journal = {The EMBO Journal}, keywords = {5-htreceptor, arrestin, grk}, month = {August}, number = {18}, pages = {2706--2718}, posted-at = {2009-09-24 02:40:42}, priority = {3}, publisher = {Nature Publishing Group}, title = {|[beta]|-arrestin1 phosphorylation by GRK5 regulates G protein-independent 5-HT4 receptor signalling}, url = {http://dx.doi.org/10.1038/emboj.2009.215}, volume = {28}, year = {2009} }

TY - JOUR ID - citeulike:5391421 L3 - citeulike-article-id:5391421 N2 - 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 Gs 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 –arrestin1 to a phosphorylated serine/threonine cluster located within the receptor C-t domain and the phosphorylation, by GRK5, of –arrestin1 (at Ser412) bound to the receptor. Phosphorylated -arrestin1 in turn prevented activation of Src constitutively bound to 5-HT4Rs, a necessary step in receptor-stimulated ERK signalling. This is the first demonstration that -arrestin1 phosphorylation by GRK5 regulates G protein-independent signalling. IS - 18 JF - The EMBO Journal SN - 0261-4189 EP - 2718 TI - |[beta]|-arrestin1 phosphorylation by GRK5 regulates G protein-independent 5-HT4 receptor signalling PB - Nature Publishing Group VL - 28 SP - 2706 KW - 5-htreceptor KW - arrestin KW - grk AU - Barthet, Gael AU - Carrat, Gaelle AU - Cassier, Elizabeth AU - Barker, Breann AU - Gaven, Florence AU - Pillot, Marion AU - Framery, Berenice AU - Pellissier, Lucie AU - Augier, Julie AU - Kang, Dong AU - Claeysen, Sylvie AU - Reiter, Eric AU - Baneres, Jean-Louis AU - Benovic, Jeffrey AU - Marin, Philippe AU - Bockaert, Joel AU - Dumuis, Aline PY - 2009/08/06/ UR - http://dx.doi.org/10.1038/emboj.2009.215 ER -