dc.contributor.author | Rathmell, Jeffrey C. | |
dc.date.accessioned | 2020-04-10T17:48:18Z | |
dc.date.available | 2020-04-10T17:48:18Z | |
dc.date.issued | 2019-03-27 | |
dc.identifier.citation | Sinclair, L. V., Howden, A. J., Brenes, A., Spinelli, L., Hukelmann, J. L., Macintyre, A. N., Liu, X., Thomson, S., Taylor, P. M., Rathmell, J. C., Locasale, J. W., Lamond, A. I., & Cantrell, D. A. (2019). Antigen receptor control of methionine metabolism in T cells. eLife, 8, e44210. https://doi.org/10.7554/eLife.44210 | en_US |
dc.identifier.issn | 2050-084X | |
dc.identifier.uri | http://hdl.handle.net/1803/9916 | |
dc.description | Only Vanderbilt University affiliated authors are listed on VUIR. For a full list of authors, access the version of record at https://elifesciences.org/articles/44210 | en_US |
dc.description.abstract | Immune activated T lymphocytes modulate the activity of key metabolic pathways to support the transcriptional reprograming and reshaping of cell proteomes that permits effector T cell differentiation. The present study uses high resolution mass spectrometry and metabolic labelling to explore how murine T cells control the methionine cycle to produce methyl donors for protein and nucleotide methylations. We show that antigen receptor engagement controls flux through the methionine cycle and RNA and histone methylations. We establish that the main rate limiting step for protein synthesis and the methionine cycle is control of methionine transporter expression. Only T cells that respond to antigen to upregulate and sustain methionine transport are supplied with methyl donors that permit the dynamic nucleotide methylations and epigenetic reprogramming that drives T cell differentiation. These data highlight how the regulation of methionine transport licenses use of methionine for multiple fundamental processes that drive T lymphocyte proliferation and differentiation. | en_US |
dc.description.sponsorship | Wellcome Trust 105024/Z/14/Z (Wellcome Trust Strategic Award) Angus I Lamond Doreen A Cantrell
Wellcome Trust 202950/Z/16/Z (Wellcome Trust Equipment Award) Doreen A Cantrell
Wellcome Trust 205023/Z/16/Z (Principal Research Fellowship) Doreen A Cantrell
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication. | en_US |
dc.language.iso | en_US | en_US |
dc.publisher | eLife | en_US |
dc.rights | © 2019, Sinclair et al.
This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited. | |
dc.rights.uri | https://elifesciences.org/articles/44210 | |
dc.subject | HIGH-RESOLUTION METABOLOMICS | en_US |
dc.subject | DNA METHYLTRANSFERASE 3A | en_US |
dc.subject | EPIGENETIC CONTROL | en_US |
dc.subject | METHYLATION | en_US |
dc.subject | EFFECTOR | en_US |
dc.subject | DIFFERENTIATION | en_US |
dc.subject | MTOR | en_US |
dc.subject | EXPRESSION | en_US |
dc.subject | MAINTENANCE | en_US |
dc.subject | TRANSPORTER | en_US |
dc.title | Antigen receptor control of methionine metabolism in T cells | en_US |
dc.type | Article | en_US |
dc.identifier.doi | 10.7554/eLife.44210 | |