Basal LAT-diacylglycerol-RasGRP1 Signals in T Cells Maintain TCRα Gene Expression

In contrast to the well-characterized T cell receptor (TCR) signaling pathways that induce genes that drive T cell development or polarization of naïve CD4 T cells into the diverse TH1, TH2, TH17 and Treg lineages, it is unclear what signals maintain specific gene expression in mature resting T cell...

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Main Authors:	Markegard, Evan, Trager, Evan, Yang, Chih-wen Ou, Zhang, Weiguo, Weiss, Arthur, Roose, Jeroen P.
Format:	Online
Language:	English
Published:	Public Library of Science 2011
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3180458/

id	pubmed-3180458
recordtype	oai_dc
spelling	pubmed-31804582011-09-30 Basal LAT-diacylglycerol-RasGRP1 Signals in T Cells Maintain TCRα Gene Expression Markegard, Evan Trager, Evan Yang, Chih-wen Ou Zhang, Weiguo Weiss, Arthur Roose, Jeroen P. Research Article In contrast to the well-characterized T cell receptor (TCR) signaling pathways that induce genes that drive T cell development or polarization of naïve CD4 T cells into the diverse TH1, TH2, TH17 and Treg lineages, it is unclear what signals maintain specific gene expression in mature resting T cells. Resting T cells residing in peripheral lymphoid organs exhibit low-level constitutive signaling. Whereas tonic signals in B cells are known to be critical for survival, the roles of tonic signals in peripheral T cells are unknown. Here we demonstrate that constitutive signals in Jurkat T cell lines are transduced via the adapter molecule LAT and the Ras exchange factor RasGRP1 to maintain expression of TCRα mRNA and surface expression of the TCR/CD3 complex. Independent approaches of reducing basal activity through the LAT-diacylglycerol-RasGRP pathway led to reduced constitutive Ras-MEK-ERK signals and decreased TCRα mRNA and surface TCR expression in Jurkat cells. However, loss of TCR expression takes several days in these cell line experiments. In agreement with these in vitro approaches, inducible deletion of Lat in vivo results in reduced TCRα mRNA- and surface TCR- expression in a delayed temporal manner as well. Lastly, we demonstrate that loss of basal LAT-RasGRP signals appears to lead to silencing or repression of TCRα transcription. We postulate that basal LAT-diacylglycerol-RasGRP signals fulfill a regulatory function in peripheral T lymphocytes by maintaining proper gene expression programs. Public Library of Science 2011-09-26 /pmc/articles/PMC3180458/ /pubmed/21966541 http://dx.doi.org/10.1371/journal.pone.0025540 Text en Markegard et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Markegard, Evan Trager, Evan Yang, Chih-wen Ou Zhang, Weiguo Weiss, Arthur Roose, Jeroen P.
spellingShingle	Markegard, Evan Trager, Evan Yang, Chih-wen Ou Zhang, Weiguo Weiss, Arthur Roose, Jeroen P. Basal LAT-diacylglycerol-RasGRP1 Signals in T Cells Maintain TCRα Gene Expression
author_facet	Markegard, Evan Trager, Evan Yang, Chih-wen Ou Zhang, Weiguo Weiss, Arthur Roose, Jeroen P.
author_sort	Markegard, Evan
title	Basal LAT-diacylglycerol-RasGRP1 Signals in T Cells Maintain TCRα Gene Expression
title_short	Basal LAT-diacylglycerol-RasGRP1 Signals in T Cells Maintain TCRα Gene Expression
title_full	Basal LAT-diacylglycerol-RasGRP1 Signals in T Cells Maintain TCRα Gene Expression
title_fullStr	Basal LAT-diacylglycerol-RasGRP1 Signals in T Cells Maintain TCRα Gene Expression
title_full_unstemmed	Basal LAT-diacylglycerol-RasGRP1 Signals in T Cells Maintain TCRα Gene Expression
title_sort	basal lat-diacylglycerol-rasgrp1 signals in t cells maintain tcrα gene expression
description	In contrast to the well-characterized T cell receptor (TCR) signaling pathways that induce genes that drive T cell development or polarization of naïve CD4 T cells into the diverse TH1, TH2, TH17 and Treg lineages, it is unclear what signals maintain specific gene expression in mature resting T cells. Resting T cells residing in peripheral lymphoid organs exhibit low-level constitutive signaling. Whereas tonic signals in B cells are known to be critical for survival, the roles of tonic signals in peripheral T cells are unknown. Here we demonstrate that constitutive signals in Jurkat T cell lines are transduced via the adapter molecule LAT and the Ras exchange factor RasGRP1 to maintain expression of TCRα mRNA and surface expression of the TCR/CD3 complex. Independent approaches of reducing basal activity through the LAT-diacylglycerol-RasGRP pathway led to reduced constitutive Ras-MEK-ERK signals and decreased TCRα mRNA and surface TCR expression in Jurkat cells. However, loss of TCR expression takes several days in these cell line experiments. In agreement with these in vitro approaches, inducible deletion of Lat in vivo results in reduced TCRα mRNA- and surface TCR- expression in a delayed temporal manner as well. Lastly, we demonstrate that loss of basal LAT-RasGRP signals appears to lead to silencing or repression of TCRα transcription. We postulate that basal LAT-diacylglycerol-RasGRP signals fulfill a regulatory function in peripheral T lymphocytes by maintaining proper gene expression programs.
publisher	Public Library of Science
publishDate	2011
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3180458/
_version_	1611477481789849600

Basal LAT-diacylglycerol-RasGRP1 Signals in T Cells Maintain TCRα Gene Expression

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