Development of a screening strategy for new modulators of T cell receptor signaling and T cell activation

Abstract Activation of the T cell receptor (TCR) leads to the generation of a network of signaling events critical to the developmental decision making and activation of T cells. Various experimental approaches continue to identify new signaling molecules, adaptor proteins, and other regulators of T...

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Autores principales:	Elijah W. Chen, Joanna Brzostek, Nicholas R. J. Gascoigne, Vasily Rybakin
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/dec67ebcd38c40508545f17c505764fa
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spelling	oai:doaj.org-article:dec67ebcd38c40508545f17c505764fa2021-12-02T15:08:04ZDevelopment of a screening strategy for new modulators of T cell receptor signaling and T cell activation10.1038/s41598-018-28106-52045-2322https://doaj.org/article/dec67ebcd38c40508545f17c505764fa2018-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-28106-5https://doaj.org/toc/2045-2322Abstract Activation of the T cell receptor (TCR) leads to the generation of a network of signaling events critical to the developmental decision making and activation of T cells. Various experimental approaches continue to identify new signaling molecules, adaptor proteins, and other regulators of TCR signaling. We propose a screening strategy for the identification of small molecules affecting TCR signaling based on the uncoupling of TCR stimulation from cellular responses in developing thymocytes. We demonstrate that this strategy successfully identifies inhibitors of kinases already shown to act downstream of TCR engagement, as well as new inhibitors. The proposed strategy is easily scalable for high throughput screening and will contribute to the identification of new druggable targets in T cell activation.Elijah W. ChenJoanna BrzostekNicholas R. J. GascoigneVasily RybakinNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-9 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Elijah W. Chen Joanna Brzostek Nicholas R. J. Gascoigne Vasily Rybakin Development of a screening strategy for new modulators of T cell receptor signaling and T cell activation
description	Abstract Activation of the T cell receptor (TCR) leads to the generation of a network of signaling events critical to the developmental decision making and activation of T cells. Various experimental approaches continue to identify new signaling molecules, adaptor proteins, and other regulators of TCR signaling. We propose a screening strategy for the identification of small molecules affecting TCR signaling based on the uncoupling of TCR stimulation from cellular responses in developing thymocytes. We demonstrate that this strategy successfully identifies inhibitors of kinases already shown to act downstream of TCR engagement, as well as new inhibitors. The proposed strategy is easily scalable for high throughput screening and will contribute to the identification of new druggable targets in T cell activation.
format	article
author	Elijah W. Chen Joanna Brzostek Nicholas R. J. Gascoigne Vasily Rybakin
author_facet	Elijah W. Chen Joanna Brzostek Nicholas R. J. Gascoigne Vasily Rybakin
author_sort	Elijah W. Chen
title	Development of a screening strategy for new modulators of T cell receptor signaling and T cell activation
title_short	Development of a screening strategy for new modulators of T cell receptor signaling and T cell activation
title_full	Development of a screening strategy for new modulators of T cell receptor signaling and T cell activation
title_fullStr	Development of a screening strategy for new modulators of T cell receptor signaling and T cell activation
title_full_unstemmed	Development of a screening strategy for new modulators of T cell receptor signaling and T cell activation
title_sort	development of a screening strategy for new modulators of t cell receptor signaling and t cell activation
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/dec67ebcd38c40508545f17c505764fa
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Development of a screening strategy for new modulators of T cell receptor signaling and T cell activation

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