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

Abstract

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.

Authors:
; ; ; ; ;
Publication Date:
Research Org.:
Brookhaven National Laboratory (BNL) National Synchrotron Light Source
Sponsoring Org.:
Doe - Office Of Science
OSTI Identifier:
930024
Report Number(s):
BNL-80638-2008-JA
TRN: US200822%%1260
DOE Contract Number:
DE-AC02-98CH10886
Resource Type:
Journal Article
Resource Relation:
Journal Name: Molecular Cell; Journal Volume: 27; Journal Issue: 3
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES; ANTIGENS; ENZYME ACTIVITY; ENZYMES; GENE MUTATIONS; IN VITRO; INHIBITION; PHOSPHATASES; PHOSPHOTRANSFERASES; PROTEINS; RECEPTORS; RESIDUES; STIMULI; TYROSINE; national synchrotron light source

Citation Formats

Mikhailik,A., Ford, B., Keller, J., Chen, Y., Nassar, N., and Carpino, N.. A Phosphatase Activity of Sts-1 Contributes to the Suppression of TCR Signaling. United States: N. p., 2007. Web. doi:10.1016/j.molcel.2007.06.015.
Mikhailik,A., Ford, B., Keller, J., Chen, Y., Nassar, N., & Carpino, N.. A Phosphatase Activity of Sts-1 Contributes to the Suppression of TCR Signaling. United States. doi:10.1016/j.molcel.2007.06.015.
Mikhailik,A., Ford, B., Keller, J., Chen, Y., Nassar, N., and Carpino, N.. Mon . "A Phosphatase Activity of Sts-1 Contributes to the Suppression of TCR Signaling". United States. doi:10.1016/j.molcel.2007.06.015.
@article{osti_930024,
title = {A Phosphatase Activity of Sts-1 Contributes to the Suppression of TCR Signaling},
author = {Mikhailik,A. and Ford, B. and Keller, J. and Chen, Y. and Nassar, N. and Carpino, N.},
abstractNote = {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.},
doi = {10.1016/j.molcel.2007.06.015},
journal = {Molecular Cell},
number = 3,
volume = 27,
place = {United States},
year = {Mon Jan 01 00:00:00 EST 2007},
month = {Mon Jan 01 00:00:00 EST 2007}
}
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