Regulation of ZAP-70 activation and TCR signaling by two related proteins, Sts-1 and Sts-2

被引：140
作者：
Carpino, N
Turner, S
Mekala, D
Takahashi, Y
Zang, HS
Geiger, TL
Doherty, P
Ihle, JN
机构：
[1] St Jude Childrens Res Hosp, Dept Biochem, Memphis, TN 38105 USA
[2] St Jude Childrens Res Hosp, Dept Immunol, Memphis, TN 38105 USA
[3] St Jude Childrens Res Hosp, Dept Pathol, Memphis, TN 38105 USA
[4] St Jude Childrens Res Hosp, Howard Hughes Med Inst, Memphis, TN 38105 USA
来源：
IMMUNITY | 2004年 / 20卷 / 01期
关键词：
D O I：
10.1016/S1074-7613(03)00351-0
中图分类号：
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号：
100102 ;
摘要：
T cells play a central role in the recognition and elimination of foreign pathogens. Signals through the T cell receptor (TCR) control the extent and duration of the T cell response. To ensure that T cells are not inappropriately activated, signaling pathways downstream of the TCR are subject to multiple levels of positive and negative regulation. Herein, we describe two related proteins, Sts-1 and Sts-2, that negatively regulate TCR signaling. T cells from mice lacking Sts-1 and Sts-2 are hyperresponsive to TCR stimulation. The phenotype is accompanied by increased Zap-70 phosphorylation and activation, including its ubiquitinylated forms. Additionally, hyperactivation of signaling proteins downstream of the TCR, a marked increase in cytokine production by Sts1/2(-/-) T cells, and increased susceptibility to autoimmunity in a mouse model of multiple sclerosis is observed. Therefore, Sts-1 and Sts-2 are critical regulators of the signaling pathways that regulate T cell activation.
引用
收藏
页码：37 / 46
页数：10
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