A Phosphatase Activity of Sts-1 Contributes to the Suppression of TCR Signaling

• Published in: Molecular cell Vol. 27; no. 3; pp. 486 - 497
• Main Authors: Mikhailik, Anatoly, Ford, Bradley, Keller, James, Chen, Yunting, Nassar, Nicolas, Carpino, Nick
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 03.08.2007
• Subjects: Animals; Blotting, Western; Cell Differentiation - physiology; Cells, Cultured; Down-Regulation - physiology; Humans; Immunoprecipitation; Mice; Mice, Knockout; MOLIMMUNO; Point Mutation; Protein Tyrosine Phosphatases - metabolism; Receptors, Antigen, T-Cell - antagonists & inhibitors; Receptors, Antigen, T-Cell - metabolism; Receptors, Antigen, T-Cell - physiology; Signal Transduction - physiology; SIGNALING; T-Lymphocytes - physiology; ZAP-70 Protein-Tyrosine Kinase - genetics; ZAP-70 Protein-Tyrosine Kinase - metabolism; MOLIMMUNO; SIGNALING
• ISSN: 1097-2765; 1097-4164
• DOI: 10.1016/j.molcel.2007.06.015

Precise signaling by the T cell receptor (TCR) is crucial for a proper immune response. To ensure that T cells respond appropriately to antigenic stimuli, TCR signaling pathways are subject to multiple levels of regulation. Sts-1 negatively regulates signaling pathways downstream of the TCR by an unknown mechanism(s). Here, we demonstrate that Sts-1 is a phosphatase that can target the tyrosine kinase Zap-70 among other proteins. The X-ray structure of the Sts-1 C terminus reveals that it has homology to members of the phosphoglycerate mutase/acid phosphatase (PGM/AcP) family of enzymes, with residues known to be important for PGM/AcP catalytic activity conserved in nature and position in Sts-1. Point mutations that impair Sts-1 phosphatase activity in vitro also impair the ability of Sts-1 to regulate TCR signaling in T cells. These observations reveal a PGM/AcP-like enzyme activity involved in the control of antigen receptor signaling.