{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T10:09:06Z","timestamp":1791281346866,"version":"4.1.0"},"reference-count":34,"publisher":"The Company of Biologists","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,1,15]]},"abstract":"<jats:title>Summary<\/jats:title>\n               <jats:p>Despite intensive investigation over the past 20 years, the specific role played by individual Gi protein family members in mediating complex cellular effects is still largely unclear. Therefore, we investigated the role of specific Gi proteins in mediating somatostatin (SS) effects in somatotroph cells. Because our previous data showed that SS receptor type 5 (SST5) carrying a spontaneous R240W mutation in the third intracellular loop had a similar ability to inhibit intracellular cAMP levels to the wild-type protein but failed to mediate inhibition of growth hormone (GH) release and cell proliferation, we used this model to check specific receptor\u2013G-protein coupling by a bioluminescent resonance energy transfer analysis. In HEK293 cells, wild-type SST5 stimulated the activation of G\u03b1i1\u20133 and G\u03b1oA, B, whereas R240W SST5 maintained the ability to activate G\u03b1i1\u20133 and G\u03b1oB, but failed to activate the splicing variant G\u03b1oA. To investigate the role of the selective deficit in G\u03b1oA coupling, we co-transfected human adenomatous somatotrophs with SST5 and a pertussis toxin (PTX)-resistant G\u03b1oA (G\u03b1oA(PTX-r)) protein. In PTX-treated cells, G\u03b1oA(PTX-r) rescued the ability of the selective SST5 analog BIM23206 to inhibit extracellular signal-related kinase 1\/2 (ERK1\/2) phosphorylation, GH secretion and intracellular cAMP levels. Moreover, we demonstrated that silencing of G\u03b1oA completely abolished SST5-mediated inhibitory effects on GH secretion and ERK1\/2 phosphorylation, but not on cAMP levels. In conclusion, by analysing the coupling specificity of human SST5 to individual G\u03b1i and G\u03b1o subunits, we identified a crucial role for G\u03b1oA signalling in human pituitary cells.<\/jats:p>","DOI":"10.1242\/jcs.116434","type":"journal-article","created":{"date-parts":[[2012,11,24]],"date-time":"2012-11-24T04:21:16Z","timestamp":1353730876000},"page":"638-644","source":"Crossref","is-referenced-by-count":26,"title":["Specific roles of Gi protein family members revealed by dissecting SST5 coupling in human pituitary cells"],"prefix":"10.1242","volume":"126","author":[{"given":"Erika","family":"Peverelli","sequence":"first","affiliation":[{"name":"Endocrinology and Diabetology Unit, Department of Clinical Sciences and Community Health, University of Milan, Fondazione IRCCS Ca' Granda Policlinico, 20122-Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Busnelli","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience, CNR, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleonora","family":"Vitali","sequence":"additional","affiliation":[{"name":"Endocrinology and Diabetology Unit, Department of Clinical Sciences and Community Health, University of Milan, Fondazione IRCCS Ca' Granda Policlinico, 20122-Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Giardino","sequence":"additional","affiliation":[{"name":"Endocrinology and Diabetology Unit, Department of Clinical Sciences and Community Health, University of Milan, Fondazione IRCCS Ca' Granda Policlinico, 20122-Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celine","family":"Gal\u00e9s","sequence":"additional","affiliation":[{"name":"Institute des Maladies Metaboliques et Cardiovasculaires, INSERM, U1048, Universite, Toulouse III Paul Sabatier, Centre Hospitalier Universitaire de Toulouse, Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea G.","family":"Lania","sequence":"additional","affiliation":[{"name":"Endocrinology and Diabetology Unit, Department of Clinical Sciences and Community Health, University of Milan, Fondazione IRCCS Ca' Granda Policlinico, 20122-Milan, Italy"},{"name":"Endocrine Unit, IRCCS Humanitas Clinical Institute, University of Milan, Rozzano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Beck-Peccoz","sequence":"additional","affiliation":[{"name":"Endocrinology and Diabetology Unit, Department of Clinical Sciences and Community Health, University of Milan, Fondazione IRCCS Ca' Granda Policlinico, 20122-Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bice","family":"Chini","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience, CNR, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanna","family":"Mantovani","sequence":"additional","affiliation":[{"name":"Endocrinology and Diabetology Unit, Department of Clinical Sciences and Community Health, University of Milan, Fondazione IRCCS Ca' Granda Policlinico, 20122-Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Spada","sequence":"additional","affiliation":[{"name":"Endocrinology and Diabetology Unit, Department of Clinical Sciences and Community Health, University of Milan, Fondazione IRCCS Ca' Granda Policlinico, 20122-Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","reference":[{"key":"2021111216305902400_b1","doi-asserted-by":"publisher","first-page":"482","DOI":"10.1530\/eje.0.1370482","article-title":"Immunodetection of G proteins in human pituitary adenomas: evidence for a low expression of proteins of the Gi subfamily.","volume":"137","author":"Ballar\u00e9","year":"1997","journal-title":"Eur. 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