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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


  • Carpino N
  • Turner S
  • Mekala D
  • Takahashi Y
  • Zang H
  • Geiger TL
  • Doherty P
  • Ihle JN



Publication Data

January 23, 2004

Associated Grants

  • Agency: NCI NIH HHS, Id: 5-F32-CA83269
  • Agency: NCI NIH HHS, Id: CA21765
  • Agency: NHLBI NIH HHS, Id: P01 HL53749
  • Agency: NIDDK NIH HHS, Id: R01 DK 42932

Mesh Terms

  • 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