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SHP2-interacting Transmembrane Adaptor Protein (SIT), A Novel Disulfide-linked Dimer Regulating Human T Cell Activation

T lymphocytes express several low molecular weight transmembrane adaptor proteins that recruit src homology (SH)2 domain–containing intracellular molecules to the cell membrane via tyrosine-based signaling motifs. We describe here a novel molecule of this group termed SIT (SHP2 interacting transmemb...

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Autores principales: Marie-Cardine, Anne, Kirchgessner, Henning, Bruyns, Eddy, Shevchenko, Andrej, Mann, Matthias, Autschbach, Frank, Ratnofsky, Sheldon, Meuer, Stefan, Schraven, Burkhart
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 1999
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193021/
https://www.ncbi.nlm.nih.gov/pubmed/10209036
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author Marie-Cardine, Anne
Kirchgessner, Henning
Bruyns, Eddy
Shevchenko, Andrej
Mann, Matthias
Autschbach, Frank
Ratnofsky, Sheldon
Meuer, Stefan
Schraven, Burkhart
author_facet Marie-Cardine, Anne
Kirchgessner, Henning
Bruyns, Eddy
Shevchenko, Andrej
Mann, Matthias
Autschbach, Frank
Ratnofsky, Sheldon
Meuer, Stefan
Schraven, Burkhart
author_sort Marie-Cardine, Anne
collection PubMed
description T lymphocytes express several low molecular weight transmembrane adaptor proteins that recruit src homology (SH)2 domain–containing intracellular molecules to the cell membrane via tyrosine-based signaling motifs. We describe here a novel molecule of this group termed SIT (SHP2 interacting transmembrane adaptor protein). SIT is a disulfide-linked homodimeric glycoprotein that is expressed in lymphocytes. After tyrosine phosphorylation by src and possibly syk protein tyrosine kinases SIT recruits the SH2 domain–containing tyrosine phosphatase SHP2 via an immunoreceptor tyrosine-based inhibition motif. Overexpression of SIT in Jurkat cells downmodulates T cell receptor– and phytohemagglutinin-mediated activation of the nuclear factor of activated T cells (NF-AT) by interfering with signaling processes that are probably located upstream of activation of phospholipase C. However, binding of SHP2 to SIT is not required for inhibition of NF-AT induction, suggesting that SIT not only regulates NF-AT activity but also controls NF-AT unrelated pathways of T cell activation involving SHP2.
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spelling pubmed-21930212008-04-16 SHP2-interacting Transmembrane Adaptor Protein (SIT), A Novel Disulfide-linked Dimer Regulating Human T Cell Activation Marie-Cardine, Anne Kirchgessner, Henning Bruyns, Eddy Shevchenko, Andrej Mann, Matthias Autschbach, Frank Ratnofsky, Sheldon Meuer, Stefan Schraven, Burkhart J Exp Med Articles T lymphocytes express several low molecular weight transmembrane adaptor proteins that recruit src homology (SH)2 domain–containing intracellular molecules to the cell membrane via tyrosine-based signaling motifs. We describe here a novel molecule of this group termed SIT (SHP2 interacting transmembrane adaptor protein). SIT is a disulfide-linked homodimeric glycoprotein that is expressed in lymphocytes. After tyrosine phosphorylation by src and possibly syk protein tyrosine kinases SIT recruits the SH2 domain–containing tyrosine phosphatase SHP2 via an immunoreceptor tyrosine-based inhibition motif. Overexpression of SIT in Jurkat cells downmodulates T cell receptor– and phytohemagglutinin-mediated activation of the nuclear factor of activated T cells (NF-AT) by interfering with signaling processes that are probably located upstream of activation of phospholipase C. However, binding of SHP2 to SIT is not required for inhibition of NF-AT induction, suggesting that SIT not only regulates NF-AT activity but also controls NF-AT unrelated pathways of T cell activation involving SHP2. The Rockefeller University Press 1999-04-19 /pmc/articles/PMC2193021/ /pubmed/10209036 Text en This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Articles
Marie-Cardine, Anne
Kirchgessner, Henning
Bruyns, Eddy
Shevchenko, Andrej
Mann, Matthias
Autschbach, Frank
Ratnofsky, Sheldon
Meuer, Stefan
Schraven, Burkhart
SHP2-interacting Transmembrane Adaptor Protein (SIT), A Novel Disulfide-linked Dimer Regulating Human T Cell Activation
title SHP2-interacting Transmembrane Adaptor Protein (SIT), A Novel Disulfide-linked Dimer Regulating Human T Cell Activation
title_full SHP2-interacting Transmembrane Adaptor Protein (SIT), A Novel Disulfide-linked Dimer Regulating Human T Cell Activation
title_fullStr SHP2-interacting Transmembrane Adaptor Protein (SIT), A Novel Disulfide-linked Dimer Regulating Human T Cell Activation
title_full_unstemmed SHP2-interacting Transmembrane Adaptor Protein (SIT), A Novel Disulfide-linked Dimer Regulating Human T Cell Activation
title_short SHP2-interacting Transmembrane Adaptor Protein (SIT), A Novel Disulfide-linked Dimer Regulating Human T Cell Activation
title_sort shp2-interacting transmembrane adaptor protein (sit), a novel disulfide-linked dimer regulating human t cell activation
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193021/
https://www.ncbi.nlm.nih.gov/pubmed/10209036
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