Details

Autor(en) / Beteiligte

• Carpino, Nick
• Turner, Steve
• Mekala, Divya
• Takahashi, Yutaka
• Zang, Heesuk
• Geiger, Terrence L.
• Doherty, Peter
• Ihle, James N.

Titel

Regulation of ZAP-70 Activation and TCR Signaling by Two Related Proteins, Sts-1 and Sts-2

Ist Teil von

• Immunity (Cambridge, Mass.), 2004, Vol.20 (1), p.37-46

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2004

Quelle

ScienceDirect

Beschreibungen/Notizen

• 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.