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However, the molecular mechanisms of their actions remain poorly understood. In this study, we investigated phosphosignaling dynamics in pituitary GH1 cells affected by TRH and TAL and the putative role of \u03b2-arrestin2 in mediating these effects. Our results revealed widespread alterations in many phosphosignaling pathways involving signal transduction via small GTPases, MAP kinases, Ser\/Thr- and Tyr-protein kinases, Wnt\/\u03b2-catenin, and members of the Hippo pathway. The differential TRH- or TAL-induced phosphorylation of numerous proteins suggests that these ligands exhibit some degree of biased agonism at the TRH receptor. The different phosphorylation patterns induced by TRH or TAL in \u03b2-arrestin2-deficient cells suggest that the \u03b2-arrestin2 scaffold is a key factor determining phosphorylation events after TRH receptor activation. Our results suggest that compounds that modulate kinase and phosphatase activity can be considered as additional adjuvants to enhance the potential therapeutic value of TRH or TAL.<\/jats:p>","DOI":"10.3390\/cells11091473","type":"journal-article","created":{"date-parts":[[2022,4,27]],"date-time":"2022-04-27T13:40:57Z","timestamp":1651066857000},"page":"1473","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["\u03b2-Arrestin2 Is Critically Involved in the Differential Regulation of Phosphosignaling Pathways by Thyrotropin-Releasing Hormone and Taltirelin"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3539-6634","authenticated-orcid":false,"given":"Zdenka","family":"Drastichova","sequence":"first","affiliation":[{"name":"Department of Physiology, Faculty of Science, Charles University, 128 00 Prague, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Radka","family":"Trubacova","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Science, Charles University, 128 00 Prague, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6372-0131","authenticated-orcid":false,"given":"Jiri","family":"Novotny","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Science, Charles University, 128 00 Prague, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1016\/0006-291X(71)90644-9","article-title":"Thyrotropin releasing hormone\u2013direct evicence for stimulation of prolactin production by pituitary cells in culture","volume":"43","author":"Tashjian","year":"1971","journal-title":"Biochem. 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