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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...

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Autores principales: 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
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2000
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.
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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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