Immunity. 2004 Jan;20(1):37-46
Carpino N, Turner S, Mekala D, Takahashi Y, Zang H, Geiger TL, Doherty P, Ihle JN.
Department of Biochemistry, Saint Jude Children's Research Hospital, 38105, Memphis, TN, USA
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.