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Title: The Sts Proteins Target Tyrosine Phosphorylated, Ubiquitinated Proteins within TCR Signaling Pathways

Abstract

The T cell receptor (TCR) detects the presence of infectious pathogens and activates numerous intracellular signaling pathways. Protein tyrosine phosphorylation and ubiquitination serve as key regulatory mechanisms downstream of the TCR. Negative regulation of TCR signaling pathways is important in controlling the immune response, and the Suppressor of TCR Signaling proteins (Sts-1 and Sts-2) have been shown to function as critical negative regulators of TCR signaling. Although their mechanism of action has yet to be fully uncovered, it is known that the Sts proteins possess intrinsic phosphatase activity. Here, we demonstrate that Sts-1 and Sts-2 are instrumental in down-modulating proteins that are dually modified by both protein tyrosine phosphorylation and ubiquitination. Specifically, both naive and activated T cells derived from genetically engineered mice that lack the Sts proteins display strikingly elevated levels of tyrosine phosphorylated, ubiquitinated proteins following TCR stimulation. The accumulation of the dually modified proteins is transient, and in activated T cells but not naive T cells is significantly enhanced by co-receptor engagement. Our observations hint at a novel regulatory mechanism downstream of the T cell receptor.

Authors:
; ; ;
Publication Date:
Research Org.:
Brookhaven National Lab. (BNL), Upton, NY (United States). National Synchrotron Light Source
Sponsoring Org.:
DOE - OFFICE OF SCIENCE
OSTI Identifier:
1020058
Report Number(s):
BNL-95906-2011-JA
Journal ID: ISSN 0161-5890; MOIMD5; TRN: US201116%%41
DOE Contract Number:  
DE-AC02-98CH10886
Resource Type:
Journal Article
Journal Name:
Molecular Immunology
Additional Journal Information:
Journal Volume: 46; Journal Issue: 16; Journal ID: ISSN 0161-5890
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES; MICE; PATHOGENS; PHOSPHATASES; PHOSPHORYLATION; PROTEINS; REGULATIONS; STIMULATION; TARGETS; TYROSINE; national synchrotron light source

Citation Formats

Carpino, N, Chen, Y, Nassar, N, and Oh, H. The Sts Proteins Target Tyrosine Phosphorylated, Ubiquitinated Proteins within TCR Signaling Pathways. United States: N. p., 2009. Web. doi:10.1016/j.molimm.2009.08.015.
Carpino, N, Chen, Y, Nassar, N, & Oh, H. The Sts Proteins Target Tyrosine Phosphorylated, Ubiquitinated Proteins within TCR Signaling Pathways. United States. https://doi.org/10.1016/j.molimm.2009.08.015
Carpino, N, Chen, Y, Nassar, N, and Oh, H. 2009. "The Sts Proteins Target Tyrosine Phosphorylated, Ubiquitinated Proteins within TCR Signaling Pathways". United States. https://doi.org/10.1016/j.molimm.2009.08.015.
@article{osti_1020058,
title = {The Sts Proteins Target Tyrosine Phosphorylated, Ubiquitinated Proteins within TCR Signaling Pathways},
author = {Carpino, N and Chen, Y and Nassar, N and Oh, H},
abstractNote = {The T cell receptor (TCR) detects the presence of infectious pathogens and activates numerous intracellular signaling pathways. Protein tyrosine phosphorylation and ubiquitination serve as key regulatory mechanisms downstream of the TCR. Negative regulation of TCR signaling pathways is important in controlling the immune response, and the Suppressor of TCR Signaling proteins (Sts-1 and Sts-2) have been shown to function as critical negative regulators of TCR signaling. Although their mechanism of action has yet to be fully uncovered, it is known that the Sts proteins possess intrinsic phosphatase activity. Here, we demonstrate that Sts-1 and Sts-2 are instrumental in down-modulating proteins that are dually modified by both protein tyrosine phosphorylation and ubiquitination. Specifically, both naive and activated T cells derived from genetically engineered mice that lack the Sts proteins display strikingly elevated levels of tyrosine phosphorylated, ubiquitinated proteins following TCR stimulation. The accumulation of the dually modified proteins is transient, and in activated T cells but not naive T cells is significantly enhanced by co-receptor engagement. Our observations hint at a novel regulatory mechanism downstream of the T cell receptor.},
doi = {10.1016/j.molimm.2009.08.015},
url = {https://www.osti.gov/biblio/1020058}, journal = {Molecular Immunology},
issn = {0161-5890},
number = 16,
volume = 46,
place = {United States},
year = {Thu Jan 01 00:00:00 EST 2009},
month = {Thu Jan 01 00:00:00 EST 2009}
}