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Phosphoprotein Associated with Glycosphingolipid-Enriched Microdomains (Pag), a Novel Ubiquitously Expressed Transmembrane Adaptor Protein, Binds the Protein Tyrosine Kinase Csk and Is Involved in Regulation of T Cell Activation
According to a recently proposed hypothesis, initiation of signal transduction via immunoreceptors depends on interactions of the engaged immunoreceptor with glycosphingolipid-enriched membrane microdomains (GEMs). In this study, we describe a novel GEM-associated transmembrane adaptor protein, term...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
2000
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2213442/ https://www.ncbi.nlm.nih.gov/pubmed/10790433 |
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author | Brdic̆ka, Tomás̆ Pavlis̆tová, Dagmar Leo, Albrecht Bruyns, Eddy Kor̆ínek, Vladimír Angelisová, Pavla Scherer, Jeanette Shevchenko, Andrej Shevchenko, Anna Hilgert, Ivan C̆erný, Jan Drbal, Karel Kuramitsu, Yasuhiro Kornacker, Birgit Hor̆ejs̆í, Václav Schraven, Burkhart |
author_facet | Brdic̆ka, Tomás̆ Pavlis̆tová, Dagmar Leo, Albrecht Bruyns, Eddy Kor̆ínek, Vladimír Angelisová, Pavla Scherer, Jeanette Shevchenko, Andrej Shevchenko, Anna Hilgert, Ivan C̆erný, Jan Drbal, Karel Kuramitsu, Yasuhiro Kornacker, Birgit Hor̆ejs̆í, Václav Schraven, Burkhart |
author_sort | Brdic̆ka, Tomás̆ |
collection | PubMed |
description | According to a recently proposed hypothesis, initiation of signal transduction via immunoreceptors depends on interactions of the engaged immunoreceptor with glycosphingolipid-enriched membrane microdomains (GEMs). In this study, we describe a novel GEM-associated transmembrane adaptor protein, termed phosphoprotein associated with GEMs (PAG). PAG comprises a short extracellular domain of 16 amino acids and a 397-amino acid cytoplasmic tail containing ten tyrosine residues that are likely phosphorylated by Src family kinases. In lymphoid cell lines and in resting peripheral blood α/β T cells, PAG is expressed as a constitutively tyrosine-phosphorylated protein and binds the major negative regulator of Src kinases, the tyrosine kinase Csk. After activation of peripheral blood α/β T cells, PAG becomes rapidly dephosphorylated and dissociates from Csk. Expression of PAG in COS cells results in recruitment of endogenous Csk, altered Src kinase activity, and impaired phosphorylation of Src-specific substrates. Moreover, overexpression of PAG in Jurkat cells downregulates T cell receptor–mediated activation of the transcription factor nuclear factor of activated T cells. These findings collectively suggest that in the absence of external stimuli, the PAG–Csk complex transmits negative regulatory signals and thus may help to keep resting T cells in a quiescent state. |
format | Text |
id | pubmed-2213442 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2000 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-22134422008-04-16 Phosphoprotein Associated with Glycosphingolipid-Enriched Microdomains (Pag), a Novel Ubiquitously Expressed Transmembrane Adaptor Protein, Binds the Protein Tyrosine Kinase Csk and Is Involved in Regulation of T Cell Activation Brdic̆ka, Tomás̆ Pavlis̆tová, Dagmar Leo, Albrecht Bruyns, Eddy Kor̆ínek, Vladimír Angelisová, Pavla Scherer, Jeanette Shevchenko, Andrej Shevchenko, Anna Hilgert, Ivan C̆erný, Jan Drbal, Karel Kuramitsu, Yasuhiro Kornacker, Birgit Hor̆ejs̆í, Václav Schraven, Burkhart J Exp Med Original Article According to a recently proposed hypothesis, initiation of signal transduction via immunoreceptors depends on interactions of the engaged immunoreceptor with glycosphingolipid-enriched membrane microdomains (GEMs). In this study, we describe a novel GEM-associated transmembrane adaptor protein, termed phosphoprotein associated with GEMs (PAG). PAG comprises a short extracellular domain of 16 amino acids and a 397-amino acid cytoplasmic tail containing ten tyrosine residues that are likely phosphorylated by Src family kinases. In lymphoid cell lines and in resting peripheral blood α/β T cells, PAG is expressed as a constitutively tyrosine-phosphorylated protein and binds the major negative regulator of Src kinases, the tyrosine kinase Csk. After activation of peripheral blood α/β T cells, PAG becomes rapidly dephosphorylated and dissociates from Csk. Expression of PAG in COS cells results in recruitment of endogenous Csk, altered Src kinase activity, and impaired phosphorylation of Src-specific substrates. Moreover, overexpression of PAG in Jurkat cells downregulates T cell receptor–mediated activation of the transcription factor nuclear factor of activated T cells. These findings collectively suggest that in the absence of external stimuli, the PAG–Csk complex transmits negative regulatory signals and thus may help to keep resting T cells in a quiescent state. The Rockefeller University Press 2000-05-01 /pmc/articles/PMC2213442/ /pubmed/10790433 Text en © 2000 The Rockefeller University Press 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 | Original Article Brdic̆ka, Tomás̆ Pavlis̆tová, Dagmar Leo, Albrecht Bruyns, Eddy Kor̆ínek, Vladimír Angelisová, Pavla Scherer, Jeanette Shevchenko, Andrej Shevchenko, Anna Hilgert, Ivan C̆erný, Jan Drbal, Karel Kuramitsu, Yasuhiro Kornacker, Birgit Hor̆ejs̆í, Václav Schraven, Burkhart Phosphoprotein Associated with Glycosphingolipid-Enriched Microdomains (Pag), a Novel Ubiquitously Expressed Transmembrane Adaptor Protein, Binds the Protein Tyrosine Kinase Csk and Is Involved in Regulation of T Cell Activation |
title | Phosphoprotein Associated with Glycosphingolipid-Enriched Microdomains (Pag), a Novel Ubiquitously Expressed Transmembrane Adaptor Protein, Binds the Protein Tyrosine Kinase Csk and Is Involved in Regulation of T Cell Activation |
title_full | Phosphoprotein Associated with Glycosphingolipid-Enriched Microdomains (Pag), a Novel Ubiquitously Expressed Transmembrane Adaptor Protein, Binds the Protein Tyrosine Kinase Csk and Is Involved in Regulation of T Cell Activation |
title_fullStr | Phosphoprotein Associated with Glycosphingolipid-Enriched Microdomains (Pag), a Novel Ubiquitously Expressed Transmembrane Adaptor Protein, Binds the Protein Tyrosine Kinase Csk and Is Involved in Regulation of T Cell Activation |
title_full_unstemmed | Phosphoprotein Associated with Glycosphingolipid-Enriched Microdomains (Pag), a Novel Ubiquitously Expressed Transmembrane Adaptor Protein, Binds the Protein Tyrosine Kinase Csk and Is Involved in Regulation of T Cell Activation |
title_short | Phosphoprotein Associated with Glycosphingolipid-Enriched Microdomains (Pag), a Novel Ubiquitously Expressed Transmembrane Adaptor Protein, Binds the Protein Tyrosine Kinase Csk and Is Involved in Regulation of T Cell Activation |
title_sort | phosphoprotein associated with glycosphingolipid-enriched microdomains (pag), a novel ubiquitously expressed transmembrane adaptor protein, binds the protein tyrosine kinase csk and is involved in regulation of t cell activation |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2213442/ https://www.ncbi.nlm.nih.gov/pubmed/10790433 |
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