Gbetagamma dimers released in response to thyrotropin activate phosphoinositide 3-kinase and regulate gene expression in thyroid cells.

Molecular Endocrinology
Miguel A ZaballosPilar Santisteban

Abstract

Signaling by TSH through its receptor leads to the dissociation of trimeric G proteins into Galpha and Gbetagamma. Galphas activates adenylyl cyclase, which increases cAMP levels that induce several effects in the thyroid cell, including transcription of the sodium-iodide symporter (NIS) gene through a mechanism involving Pax8 binding to the NIS promoter. Much less is known about the function of Gbetagamma in thyroid differentiation, and therefore we studied their role in TSH signaling. Gbetagamma overexpression inhibits NIS promoter activation and reduces NIS protein accumulation in response to TSH and forskolin. Conversely, inhibition of Gbetagamma-dependent pathways increases NIS promoter activity elicited by TSH but does not modify forskolin-induced activation. Gbetagamma dimers are being released from the Gs subfamily of proteins, because cholera toxin mimics the effects elicited by TSH, whereas pertussis toxin has no effect on NIS promoter activity. We also found that TSH stimulates Akt phosphorylation in a phosphoinositide 3-kinase (PI3K)-dependent and cAMP-independent manner. This is mediated by Gbetagamma, because its overexpression or specific sequestration, respectively, increased or reduced phosphorylated Akt levels...Continue Reading

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Citations

Feb 4, 2012·Molecular Endocrinology·Ana Chocarro-CalvoCustodia García-Jiménez
Jul 1, 2008·Expert Review of Endocrinology & Metabolism·Custodia García-Jiménez, Pilar Santisteban
Mar 11, 2011·American Journal of Physiology. Cell Physiology·Bruno M AndradeRolando B Ceddia
Mar 22, 2014·Molecular Endocrinology·Ana Sastre-Perona, Pilar Santisteban
Mar 15, 2015·Expert Opinion on Therapeutic Targets·Terry F Davies, Rauf Latif
Aug 27, 2015·Endocrine-related Cancer·Fernanda VaismanMario Vaisman
Jan 26, 2020·Journal of Clinical Medicine·Maha HichriBéatrice Cambien
Oct 17, 2015·Molecular and Cellular Biochemistry·Francisco J Rodríguez-ÁlvarezMa José Toro
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Jun 28, 2011·Expert Opinion on Therapeutic Targets·Elaine Cristina Lima de SouzaDenise Pires de Carvalho
Nov 22, 2017·Thyroid : Official Journal of the American Thyroid Association·Carlos Frederico Lima GonçalvesAndrea Claudia Freitas Ferreira
Jul 28, 2016·Thyroid : Official Journal of the American Thyroid Association·Jamile Calil-SilveiraMaria Tereza Nunes
Sep 17, 2020·Thyroid : Official Journal of the American Thyroid Association·Romina Celeste GeyselsJuan Pablo Nicola
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Jan 20, 2010·Biochimica Et Biophysica Acta·Stephan LorenzKnut Krohn

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