TY - JOUR
T1 - Regulation of ZAP-70 Activation and TCR Signaling by Two Related Proteins, Sts-1 and Sts-2
AU - Carpino, Nick
AU - Turner, Steve
AU - Mekala, Divya
AU - Takahashi, Yutaka
AU - Zang, Heesuk
AU - Geiger, Terrence L.
AU - Doherty, Peter
AU - Ihle, James N.
PY - 2004/1/1
Y1 - 2004/1/1
N2 -
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.
AB -
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.
UR - http://www.scopus.com/inward/record.url?scp=1642456674&partnerID=8YFLogxK
U2 - 10.1016/S1074-7613(03)00351-0
DO - 10.1016/S1074-7613(03)00351-0
M3 - Article
C2 - 14738763
AN - SCOPUS:1642456674
VL - 20
SP - 37
EP - 46
JO - Immunity
JF - Immunity
SN - 1074-7613
IS - 1
ER -