TRAF3 enhances TCR signaling by regulating the inhibitors Csk and PTPN22

Alicia M Wallis; Ellie C Wallace; Bruce S Hostager; Zuoan Yi; Jon C D Houtman; Gail A Bishop

doi:10.1038/s41598-017-02280-4

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TRAF3 enhances TCR signaling by regulating the inhibitors Csk and PTPN22

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Peer reviewed

TRAF3 enhances TCR signaling by regulating the inhibitors Csk and PTPN22

Alicia M Wallis, Ellie C Wallace, Bruce S Hostager, Zuoan Yi, Jon C D Houtman and Gail A Bishop

Scientific reports, Vol.7(1), pp.2081-13

05/18/2017

DOI: 10.1038/s41598-017-02280-4

PMCID: PMC5437045

PMID: 28522807

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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.

Receptors, Antigen, T-Cell - metabolism

Signal Transduction

Humans

Mice, Inbred C57BL

Protein Tyrosine Phosphatase, Non-Receptor Type 22 - metabolism

Cells, Cultured

TNF Receptor-Associated Factor 3 - metabolism

Protein Transport

Animals

T-Lymphocytes - metabolism

TNF Receptor-Associated Factor 3 - genetics

HEK293 Cells

src-Family Kinases - metabolism

Cell Line, Tumor

Protein Binding

Cell Membrane - metabolism

Mice

Details

Title: Subtitle: TRAF3 enhances TCR signaling by regulating the inhibitors Csk and PTPN22
Creators: Alicia M Wallis - Graduate Program in Immunology, Iowa City, IA, 52242, USA
Ellie C Wallace - Biomedical Engineering, Iowa City, IA, 52242, USA
Bruce S Hostager - Depts of Microbiology, Iowa City, IA, 52242, USA
Zuoan Yi - Depts of Microbiology, Iowa City, IA, 52242, USA
Jon C D Houtman - Internal Medicine, Iowa City, IA, 52242, USA
Gail A Bishop - The University of Iowa and VAMC, Iowa City, IA, 52242, USA. gail-bishop@uiowa.edu
Resource Type: Journal article
Publication Details: Scientific reports, Vol.7(1), pp.2081-13
DOI: 10.1038/s41598-017-02280-4
PMID: 28522807
PMCID: PMC5437045
NLM abbreviation: Sci Rep
ISSN: 2045-2322
eISSN: 2045-2322
Publisher: England
Grant note: P30 ES005605 / NIEHS NIH HHS P30 CA086862 / NCI NIH HHS R01 AI123107 / NIAID NIH HHS
Language: English
Date published: 05/18/2017
Academic Unit: Microbiology and Immunology; President; Internal Medicine
Record Identifier: 9984001152802771

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