TRAF3 enhances TCR signaling by regulating the inhibitors Csk and PTPN22

Abstract The adaptor protein TNF receptor associated factor (TRAF) 3 is required for effective TCR signaling and normal T cell effector functions, and associates with the CD3/CD28 complex upon activation. To determine how TRAF3 promotes proximal TCR signaling, we studied TRAF3-deficient mouse and hu...

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Autores principales:	Alicia M. Wallis, Ellie C. Wallace, Bruce S. Hostager, Zuoan Yi, Jon C. D. Houtman, Gail A. Bishop
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/193ddd2d1b1a4ac4ac05b3cd822eef66
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spelling	oai:doaj.org-article:193ddd2d1b1a4ac4ac05b3cd822eef662021-12-02T11:41:11ZTRAF3 enhances TCR signaling by regulating the inhibitors Csk and PTPN2210.1038/s41598-017-02280-42045-2322https://doaj.org/article/193ddd2d1b1a4ac4ac05b3cd822eef662017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-02280-4https://doaj.org/toc/2045-2322Abstract The adaptor protein TNF receptor associated factor (TRAF) 3 is required for effective TCR signaling and normal T cell effector functions, and associates with the CD3/CD28 complex upon activation. To determine how TRAF3 promotes proximal TCR signaling, we studied TRAF3-deficient mouse and human T cells, which showed a marked reduction in activating phosphorylation of the TCR-associated kinase Lck. The impact of TRAF3 on this very early signaling event led to the hypothesis that TRAF3 restrains one or both of two known inhibitors of Lck, C-terminal Src kinase (Csk) and protein tyrosine phosphatase N22 (PTPN22). TRAF3 associated with Csk, promoting the dissociation of Csk from the plasma membrane. TRAF3 also associated with and regulated the TCR/CD28 induced localization of PTPN22. Loss of TRAF3 resulted in increased amounts of both Csk and PTPN22 in T cell membrane fractions and decreased association of PTPN22 with Csk. These findings identify a new role for T cell TRAF3 in promoting T cell activation, by regulating localization and functions of early TCR signaling inhibitors.Alicia M. WallisEllie C. WallaceBruce S. HostagerZuoan YiJon C. D. HoutmanGail A. BishopNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Alicia M. Wallis Ellie C. Wallace Bruce S. Hostager Zuoan Yi Jon C. D. Houtman Gail A. Bishop TRAF3 enhances TCR signaling by regulating the inhibitors Csk and PTPN22
description	Abstract The adaptor protein TNF receptor associated factor (TRAF) 3 is required for effective TCR signaling and normal T cell effector functions, and associates with the CD3/CD28 complex upon activation. To determine how TRAF3 promotes proximal TCR signaling, we studied TRAF3-deficient mouse and human T cells, which showed a marked reduction in activating phosphorylation of the TCR-associated kinase Lck. The impact of TRAF3 on this very early signaling event led to the hypothesis that TRAF3 restrains one or both of two known inhibitors of Lck, C-terminal Src kinase (Csk) and protein tyrosine phosphatase N22 (PTPN22). TRAF3 associated with Csk, promoting the dissociation of Csk from the plasma membrane. TRAF3 also associated with and regulated the TCR/CD28 induced localization of PTPN22. Loss of TRAF3 resulted in increased amounts of both Csk and PTPN22 in T cell membrane fractions and decreased association of PTPN22 with Csk. These findings identify a new role for T cell TRAF3 in promoting T cell activation, by regulating localization and functions of early TCR signaling inhibitors.
format	article
author	Alicia M. Wallis Ellie C. Wallace Bruce S. Hostager Zuoan Yi Jon C. D. Houtman Gail A. Bishop
author_facet	Alicia M. Wallis Ellie C. Wallace Bruce S. Hostager Zuoan Yi Jon C. D. Houtman Gail A. Bishop
author_sort	Alicia M. Wallis
title	TRAF3 enhances TCR signaling by regulating the inhibitors Csk and PTPN22
title_short	TRAF3 enhances TCR signaling by regulating the inhibitors Csk and PTPN22
title_full	TRAF3 enhances TCR signaling by regulating the inhibitors Csk and PTPN22
title_fullStr	TRAF3 enhances TCR signaling by regulating the inhibitors Csk and PTPN22
title_full_unstemmed	TRAF3 enhances TCR signaling by regulating the inhibitors Csk and PTPN22
title_sort	traf3 enhances tcr signaling by regulating the inhibitors csk and ptpn22
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/193ddd2d1b1a4ac4ac05b3cd822eef66
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_version_	1718395447191535616

TRAF3 enhances TCR signaling by regulating the inhibitors Csk and PTPN22

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