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

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

Research output: Contribution to journalArticleResearchpeer-review

110 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)37-46
Number of pages10
JournalImmunity
Volume20
Issue number1
DOIs
Publication statusPublished - 1 Jan 2004
Externally publishedYes

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