Regulation of ZAP-70 activation and TCR signaling by two related proteins, Sts-1 and Sts-2.
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.
Pubmed ID: 14738763 RIS Download
Animals | Cell Differentiation | Down-Regulation | Encephalomyelitis, Autoimmune, Experimental | Enzyme Activation | Hematopoietic Stem Cells | Mice | Mice, Knockout | Protein-Tyrosine Kinases | Receptors, Antigen, T-Cell | Signal Transduction | T-Lymphocytes | ZAP-70 Protein-Tyrosine Kinase