title: Somatostatin activates Ras and ERK1/2 via a G protein βγ-subunit-initiated pathway in thyroid cells.
abstract: Somatostatin (SST) is one of the main regulators of thyroid function. It acts by binding to its receptors, which lead to the dissociation of G proteins into Gαi and Gβγ subunits. However, much less is known about the function of Gβγ in thyroid cells. Here, we studied the role of SST and Gβγ dimers released upon SST stimulation on the Ras-ERK1/2 pathway in FTRL-5 thyroid cells. We demonstrate that SST activates Ras through Gi proteins, since SST-induced Ras activation is inhibited by pertussis toxin. Moreover, the specific sequestration of Gβγ dimers decreases Ras-GTP and phosphorylated ERK1/2 levels, and overexpression of Gβγ increases ERK1/2 phosphorylation induced by SST, indicating that Gβγ dimers released after SST treatment mediate activation of Ras and ERK1/2. On the other hand, SST treatment does not modify the expression of the thyroid differentiation marker sodium/iodide symporter (NIS) through ERK1/2 activation. However, SST increases AKT activation and the inhibition of the Src/PI3K/AKT pathway increases NIS levels in SST-treated cells. Thus, we conclude that, in thyroid cells, signalling from SST receptors to ERK1/2 involves a Gβγ-mediated signal acting on a Ras-dependent pathway. Moreover, we demonstrate that SST might regulates NIS expression through a Src/PI3K/AKT-dependent mechanism, but not through ERK1/2 signalling, showing the main role of this hormone in thyroid function.
authors.affiliation: Departamento de Biología de Sistemas, Unidad Bioquímica y Biología Molecular. Facultad de Medicina, Universidad de Alcalá, Ctra. Madrid-Barcelona Km.33,6, 28871, Alcalá de Henares, Madrid, Spain.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Rodríguez-Álvarez
authors.affiliation: Departamento de Biología de Sistemas, Unidad Bioquímica y Biología Molecular. Facultad de Medicina, Universidad de Alcalá, Ctra. Madrid-Barcelona Km.33,6, 28871, Alcalá de Henares, Madrid, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Jiménez-Mora
authors.affiliation: Departamento de Biología de Sistemas, Unidad Bioquímica y Biología Molecular. Facultad de Medicina, Universidad de Alcalá, Ctra. Madrid-Barcelona Km.33,6, 28871, Alcalá de Henares, Madrid, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Caballero
authors.affiliation: Departamento de Biología de Sistemas, Unidad Bioquímica y Biología Molecular. Facultad de Medicina, Universidad de Alcalá, Ctra. Madrid-Barcelona Km.33,6, 28871, Alcalá de Henares, Madrid, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Gallego
authors.affiliation: Departamento de Biología de Sistemas, Unidad Bioquímica y Biología Molecular. Facultad de Medicina, Universidad de Alcalá, Ctra. Madrid-Barcelona Km.33,6, 28871, Alcalá de Henares, Madrid, Spain. antonio.chiloeches@uah.es.
authors.forename: Antonio
authors.initials: A
authors.lastname: Chiloeches
authors.affiliation: Departamento de Biología de Sistemas, Unidad Bioquímica y Biología Molecular. Facultad de Medicina, Universidad de Alcalá, Ctra. Madrid-Barcelona Km.33,6, 28871, Alcalá de Henares, Madrid, Spain. josefa.toro@uah.es.
authors.forename: Ma José
authors.initials: MJ
authors.lastname: Toro
mesh_terms: D002460:Cell Line; D044387:GTP-Binding Protein beta Subunits / Q000378:metabolism*; D044388:GTP-Binding Protein gamma Subunits / Q000378:metabolism*; D006801:Humans; D020935:MAP Kinase Signaling System; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D013004:Somatostatin / Q000008:administration & dosage*; D013961:Thyroid Gland / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018631:ras Proteins / Q000378:metabolism*
chemical_list: C118981:G-protein Beta gamma; D044387:GTP-Binding Protein beta Subunits; D044388:GTP-Binding Protein gamma Subunits; D013004:Somatostatin; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D018631:ras Proteins
keywords: ERK1/2; Gi proteins; Gβγ; Ras; Somatostatin; Thyroid