Regulation of phosphosignaling pathways involved in transcription of cell cycle target genes by TRH receptor activation in GH1 cells.

Autor: Drastichova Z; Department of Physiology, Faculty of Science, Charles University, 128 00 Prague, Czechia., Trubacova R; Department of Physiology, Faculty of Science, Charles University, 128 00 Prague, Czechia; Institute of Physiology, Czech Academy of Sciences, 142 20 Prague, Czechia., Novotny J; Department of Physiology, Faculty of Science, Charles University, 128 00 Prague, Czechia. Electronic address: jiri.novotny@natur.cuni.cz.
Jazyk: angličtina
Zdroj: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie [Biomed Pharmacother] 2023 Dec; Vol. 168, pp. 115830. Date of Electronic Publication: 2023 Nov 06.
DOI: 10.1016/j.biopha.2023.115830
Abstrakt: Thyrotropin-releasing hormone (TRH) is known to activate several cellular signaling pathway, but the activation of the TRH receptor (TRH-R) has not been reported to regulate gene transcription. The aim of this study was to identify phosphosignaling pathways and phosphoprotein complexes associated with gene transcription in GH1 pituitary cells treated with TRH or its analog, taltirelin (TAL), using label-free bottom-up mass spectrometry-based proteomics. Our detailed analysis provided insight into the mechanism through which TRH-R activation may regulate the transcription of genes related to the cell cycle and proliferation. It involves control of the signaling pathways for β-catenin/Tcf, Notch/RBPJ, p53/p21/Rbl2/E2F, Myc, and YY1/Rb1/E2F through phosphorylation and dephosphorylation of their key components. In many instances, the phosphorylation patterns of differentially phosphorylated phosphoproteins in TRH- or TAL-treated cells were identical or displayed a similar trend in phosphorylation. However, some phosphoproteins, especially components of the Wnt/β-catenin/Tcf and YY1/Rb1/E2F pathways, exhibited different phosphorylation patterns in TRH- and TAL-treated cells. This supports the notion that TRH and TAL may act, at least in part, as biased agonists. Additionally, the deficiency of β-arrestin2 resulted in a reduced number of alterations in phosphorylation, highlighting the critical role of β-arrestin2 in the signal transduction from TRH-R in the plasma membrane to transcription factors in the nucleus.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)
Databáze: MEDLINE
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