The Autoimmunity Risk Variant LYP-W620 Cooperates with CSK in the Regulation of TCR Signaling

The protein tyrosine phosphatase LYP, a key regulator of TCR signaling, presents a single nucleotide polymorphism, C1858T, associated with several autoimmune diseases such as type I diabetes, rheumatoid arthritis, and lupus. This polymorphism changes an R by a W in the P1 Pro rich motif of LYP, whic...

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Autores principales: de la Puerta, María Luisa, Trinidad, Antonio G., Rodríguez, María del Carmen, de Pereda, José María, Sánchez Crespo, Mariano, Bayón, Yolanda, Alonso, Andrés
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Research Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3554717/
https://www.ncbi.nlm.nih.gov/pubmed/23359562
http://dx.doi.org/10.1371/journal.pone.0054569
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author de la Puerta, María Luisa
Trinidad, Antonio G.
Rodríguez, María del Carmen
de Pereda, José María
Sánchez Crespo, Mariano
Bayón, Yolanda
Alonso, Andrés
author_facet de la Puerta, María Luisa
Trinidad, Antonio G.
Rodríguez, María del Carmen
de Pereda, José María
Sánchez Crespo, Mariano
Bayón, Yolanda
Alonso, Andrés
author_sort de la Puerta, María Luisa
collection PubMed
description The protein tyrosine phosphatase LYP, a key regulator of TCR signaling, presents a single nucleotide polymorphism, C1858T, associated with several autoimmune diseases such as type I diabetes, rheumatoid arthritis, and lupus. This polymorphism changes an R by a W in the P1 Pro rich motif of LYP, which binds to CSK SH3 domain, another negative regulator of TCR signaling. Based on the analysis of the mouse homologue, Pep, it was proposed that LYP and CSK bind constitutively to inhibit LCK and subsequently TCR signaling. The detailed study of LYP/CSK interaction, here presented, showed that LYP/CSK interaction was inducible upon TCR stimulation, and involved LYP P1 and P2 motifs, and CSK SH3 and SH2 domains. Abrogating LYP/CSK interaction did not preclude the regulation of TCR signaling by these proteins.
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spelling pubmed-35547172013-01-28 The Autoimmunity Risk Variant LYP-W620 Cooperates with CSK in the Regulation of TCR Signaling de la Puerta, María Luisa Trinidad, Antonio G. Rodríguez, María del Carmen de Pereda, José María Sánchez Crespo, Mariano Bayón, Yolanda Alonso, Andrés PLoS One Research Article The protein tyrosine phosphatase LYP, a key regulator of TCR signaling, presents a single nucleotide polymorphism, C1858T, associated with several autoimmune diseases such as type I diabetes, rheumatoid arthritis, and lupus. This polymorphism changes an R by a W in the P1 Pro rich motif of LYP, which binds to CSK SH3 domain, another negative regulator of TCR signaling. Based on the analysis of the mouse homologue, Pep, it was proposed that LYP and CSK bind constitutively to inhibit LCK and subsequently TCR signaling. The detailed study of LYP/CSK interaction, here presented, showed that LYP/CSK interaction was inducible upon TCR stimulation, and involved LYP P1 and P2 motifs, and CSK SH3 and SH2 domains. Abrogating LYP/CSK interaction did not preclude the regulation of TCR signaling by these proteins. Public Library of Science 2013-01-24 /pmc/articles/PMC3554717/ /pubmed/23359562 http://dx.doi.org/10.1371/journal.pone.0054569 Text en © 2013 de la Puerta et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
de la Puerta, María Luisa
Trinidad, Antonio G.
Rodríguez, María del Carmen
de Pereda, José María
Sánchez Crespo, Mariano
Bayón, Yolanda
Alonso, Andrés
The Autoimmunity Risk Variant LYP-W620 Cooperates with CSK in the Regulation of TCR Signaling
title The Autoimmunity Risk Variant LYP-W620 Cooperates with CSK in the Regulation of TCR Signaling
title_full The Autoimmunity Risk Variant LYP-W620 Cooperates with CSK in the Regulation of TCR Signaling
title_fullStr The Autoimmunity Risk Variant LYP-W620 Cooperates with CSK in the Regulation of TCR Signaling
title_full_unstemmed The Autoimmunity Risk Variant LYP-W620 Cooperates with CSK in the Regulation of TCR Signaling
title_short The Autoimmunity Risk Variant LYP-W620 Cooperates with CSK in the Regulation of TCR Signaling
title_sort autoimmunity risk variant lyp-w620 cooperates with csk in the regulation of tcr signaling
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3554717/
https://www.ncbi.nlm.nih.gov/pubmed/23359562
http://dx.doi.org/10.1371/journal.pone.0054569
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