The effector functions of mature T lymphocytes are impaired in transgenic mice expressing the SH2 domain of TSAd/Lad

Youngbong Choi; Eunkyung Park; Eunseon Ahn; Inyoung Park; Yungdae Yun

doi:10.1007/s10059-009-0121-0

The effector functions of mature T lymphocytes are impaired in transgenic mice expressing the SH2 domain of TSAd/Lad

Youngbong Choi, Eunkyung Park, Eunseon Ahn, Inyoung Park, Yungdae Yun

Research output: Contribution to journal › Article › peer-review

4 Scopus citations

Abstract

TSAd/Lad is a T cell adaptor molecule involved in p56^lck -mediated T cell activation. To investigate the functions of TSAd in T cells, we generated transgenic (TG) mice expressing the SH2 domain of TSAd (TSAd-SH2) under the control of the p56^lck proximal promoter. In T cells from TSAd-SH2 TG mice, T cell receptor (TCR)-mediated early signaling events, such as Ca²⁺ flux and ERK activation, were normal; however, late activation events, such as IL-2 production and proliferation, were significantly reduced. Moreover, TCR-induced cell adhesion to extracellular matrix (ECM) proteins and migration through ECM proteins were defective in T cells from TSAd-SH2 TG mice. Furthermore, the contact hypersensitivity (CHS) reaction, an inflammatory response mainly mediated by T helper 1 (Th1) cells, was inhibited in TSAd-SH2 TG mice. Taken together, these results show that TSAd, particularly the SH2 domain of TSAd, is essential for the effector functions of T cells.

Original language	English (US)
Pages (from-to)	183-188
Number of pages	6
Journal	Molecules and cells
Volume	28
Issue number	3
DOIs	https://doi.org/10.1007/s10059-009-0121-0
State	Published - 2009
Externally published	Yes

Keywords

Adhesion
Lad
Migration
SH2 domain
TSAd

ASJC Scopus subject areas

Molecular Biology
Cell Biology

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10.1007/s10059-009-0121-0

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title = "The effector functions of mature T lymphocytes are impaired in transgenic mice expressing the SH2 domain of TSAd/Lad",

abstract = "TSAd/Lad is a T cell adaptor molecule involved in p56lck -mediated T cell activation. To investigate the functions of TSAd in T cells, we generated transgenic (TG) mice expressing the SH2 domain of TSAd (TSAd-SH2) under the control of the p56lck proximal promoter. In T cells from TSAd-SH2 TG mice, T cell receptor (TCR)-mediated early signaling events, such as Ca2+ flux and ERK activation, were normal; however, late activation events, such as IL-2 production and proliferation, were significantly reduced. Moreover, TCR-induced cell adhesion to extracellular matrix (ECM) proteins and migration through ECM proteins were defective in T cells from TSAd-SH2 TG mice. Furthermore, the contact hypersensitivity (CHS) reaction, an inflammatory response mainly mediated by T helper 1 (Th1) cells, was inhibited in TSAd-SH2 TG mice. Taken together, these results show that TSAd, particularly the SH2 domain of TSAd, is essential for the effector functions of T cells.",

keywords = "Adhesion, Lad, Migration, SH2 domain, TSAd",

author = "Youngbong Choi and Eunkyung Park and Eunseon Ahn and Inyoung Park and Yungdae Yun",

note = "Funding Information: This work was supported in part by the Basic Research Promotion Fund (KRF-2008-C00652), Molecular and Cellular Biodis-covery Program (2006-02689), and the NCRC program (#R15- 2006-020) through the Center for Cell Signaling and Drug Discovery. This work was also supported by a grant from Ewha Womans University. I. Park was supported by the Brain Korea 21 Project.",

year = "2009",

doi = "10.1007/s10059-009-0121-0",

language = "English (US)",

volume = "28",

pages = "183--188",

journal = "Molecules and cells",

issn = "1016-8478",

publisher = "Elsevier B.V.",

number = "3",

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TY - JOUR

T1 - The effector functions of mature T lymphocytes are impaired in transgenic mice expressing the SH2 domain of TSAd/Lad

AU - Choi, Youngbong

AU - Park, Eunkyung

AU - Ahn, Eunseon

AU - Park, Inyoung

AU - Yun, Yungdae

N1 - Funding Information: This work was supported in part by the Basic Research Promotion Fund (KRF-2008-C00652), Molecular and Cellular Biodis-covery Program (2006-02689), and the NCRC program (#R15- 2006-020) through the Center for Cell Signaling and Drug Discovery. This work was also supported by a grant from Ewha Womans University. I. Park was supported by the Brain Korea 21 Project.

PY - 2009

Y1 - 2009

N2 - TSAd/Lad is a T cell adaptor molecule involved in p56lck -mediated T cell activation. To investigate the functions of TSAd in T cells, we generated transgenic (TG) mice expressing the SH2 domain of TSAd (TSAd-SH2) under the control of the p56lck proximal promoter. In T cells from TSAd-SH2 TG mice, T cell receptor (TCR)-mediated early signaling events, such as Ca2+ flux and ERK activation, were normal; however, late activation events, such as IL-2 production and proliferation, were significantly reduced. Moreover, TCR-induced cell adhesion to extracellular matrix (ECM) proteins and migration through ECM proteins were defective in T cells from TSAd-SH2 TG mice. Furthermore, the contact hypersensitivity (CHS) reaction, an inflammatory response mainly mediated by T helper 1 (Th1) cells, was inhibited in TSAd-SH2 TG mice. Taken together, these results show that TSAd, particularly the SH2 domain of TSAd, is essential for the effector functions of T cells.

AB - TSAd/Lad is a T cell adaptor molecule involved in p56lck -mediated T cell activation. To investigate the functions of TSAd in T cells, we generated transgenic (TG) mice expressing the SH2 domain of TSAd (TSAd-SH2) under the control of the p56lck proximal promoter. In T cells from TSAd-SH2 TG mice, T cell receptor (TCR)-mediated early signaling events, such as Ca2+ flux and ERK activation, were normal; however, late activation events, such as IL-2 production and proliferation, were significantly reduced. Moreover, TCR-induced cell adhesion to extracellular matrix (ECM) proteins and migration through ECM proteins were defective in T cells from TSAd-SH2 TG mice. Furthermore, the contact hypersensitivity (CHS) reaction, an inflammatory response mainly mediated by T helper 1 (Th1) cells, was inhibited in TSAd-SH2 TG mice. Taken together, these results show that TSAd, particularly the SH2 domain of TSAd, is essential for the effector functions of T cells.

KW - Adhesion

KW - Lad

KW - Migration

KW - SH2 domain

KW - TSAd

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The effector functions of mature T lymphocytes are impaired in transgenic mice expressing the SH2 domain of TSAd/Lad

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