Cargando…
Effect of Pharmacological Inhibition of the Catalytic Activity of Phosphatases of Regenerating Liver in Early T Cell Receptor Signaling Dynamics and IL-2 Production
We have previously shown the delivery of phosphatase of regenerating liver-1 (PRL-1) to the immunological synapse (IS) and proposed a regulatory role of the catalytic activity of PRLs (PRL-1, PRL-2 and PRL-3) in antigen-induced IL-2 production. Nonetheless, the expression in T cells and delivery to...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7177812/ https://www.ncbi.nlm.nih.gov/pubmed/32260565 http://dx.doi.org/10.3390/ijms21072530 |
_version_ | 1783525303900962816 |
---|---|
author | Aguilar-Sopeña, Oscar Hernández-Pérez, Sara Alegre-Gómez, Sergio Castro-Sánchez, Patricia Iglesias-Ceacero, Alba Lazo, John S. Roda-Navarro, Pedro |
author_facet | Aguilar-Sopeña, Oscar Hernández-Pérez, Sara Alegre-Gómez, Sergio Castro-Sánchez, Patricia Iglesias-Ceacero, Alba Lazo, John S. Roda-Navarro, Pedro |
author_sort | Aguilar-Sopeña, Oscar |
collection | PubMed |
description | We have previously shown the delivery of phosphatase of regenerating liver-1 (PRL-1) to the immunological synapse (IS) and proposed a regulatory role of the catalytic activity of PRLs (PRL-1, PRL-2 and PRL-3) in antigen-induced IL-2 production. Nonetheless, the expression in T cells and delivery to the IS of the highly homologous PRL-3, as well as the role of the catalytic activity of PRLs in antigen-induced early signaling, has not been investigated. Here, the expression of PRL-3 protein was detected in primary CD4 T cells and in the CD4 T cell line Jurkat (JK), in which an overexpressed GFP-PRL-3 fluorescent fusion protein trafficked through the endosomal recycling compartment and co-localized with PLCγ1 signaling sites at the IS. Pharmacological inhibition was used to compare the role of the catalytic activity of PRLs in antigen-induced early signaling and late IL-2 production. Although the phosphatase activity of PRLs was not critical for early signaling triggered by antigen, it seemed to regulate signaling dynamics and was necessary for proper IL-2 production. We propose that enzymatic activity of PRLs has a higher significance for cytokine production than for early signaling at the IS. However, further research will be necessary to deeply understand the regulatory role of PRLs during lymphocyte activation and effector function. |
format | Online Article Text |
id | pubmed-7177812 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-71778122020-04-28 Effect of Pharmacological Inhibition of the Catalytic Activity of Phosphatases of Regenerating Liver in Early T Cell Receptor Signaling Dynamics and IL-2 Production Aguilar-Sopeña, Oscar Hernández-Pérez, Sara Alegre-Gómez, Sergio Castro-Sánchez, Patricia Iglesias-Ceacero, Alba Lazo, John S. Roda-Navarro, Pedro Int J Mol Sci Communication We have previously shown the delivery of phosphatase of regenerating liver-1 (PRL-1) to the immunological synapse (IS) and proposed a regulatory role of the catalytic activity of PRLs (PRL-1, PRL-2 and PRL-3) in antigen-induced IL-2 production. Nonetheless, the expression in T cells and delivery to the IS of the highly homologous PRL-3, as well as the role of the catalytic activity of PRLs in antigen-induced early signaling, has not been investigated. Here, the expression of PRL-3 protein was detected in primary CD4 T cells and in the CD4 T cell line Jurkat (JK), in which an overexpressed GFP-PRL-3 fluorescent fusion protein trafficked through the endosomal recycling compartment and co-localized with PLCγ1 signaling sites at the IS. Pharmacological inhibition was used to compare the role of the catalytic activity of PRLs in antigen-induced early signaling and late IL-2 production. Although the phosphatase activity of PRLs was not critical for early signaling triggered by antigen, it seemed to regulate signaling dynamics and was necessary for proper IL-2 production. We propose that enzymatic activity of PRLs has a higher significance for cytokine production than for early signaling at the IS. However, further research will be necessary to deeply understand the regulatory role of PRLs during lymphocyte activation and effector function. MDPI 2020-04-05 /pmc/articles/PMC7177812/ /pubmed/32260565 http://dx.doi.org/10.3390/ijms21072530 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Communication Aguilar-Sopeña, Oscar Hernández-Pérez, Sara Alegre-Gómez, Sergio Castro-Sánchez, Patricia Iglesias-Ceacero, Alba Lazo, John S. Roda-Navarro, Pedro Effect of Pharmacological Inhibition of the Catalytic Activity of Phosphatases of Regenerating Liver in Early T Cell Receptor Signaling Dynamics and IL-2 Production |
title | Effect of Pharmacological Inhibition of the Catalytic Activity of Phosphatases of Regenerating Liver in Early T Cell Receptor Signaling Dynamics and IL-2 Production |
title_full | Effect of Pharmacological Inhibition of the Catalytic Activity of Phosphatases of Regenerating Liver in Early T Cell Receptor Signaling Dynamics and IL-2 Production |
title_fullStr | Effect of Pharmacological Inhibition of the Catalytic Activity of Phosphatases of Regenerating Liver in Early T Cell Receptor Signaling Dynamics and IL-2 Production |
title_full_unstemmed | Effect of Pharmacological Inhibition of the Catalytic Activity of Phosphatases of Regenerating Liver in Early T Cell Receptor Signaling Dynamics and IL-2 Production |
title_short | Effect of Pharmacological Inhibition of the Catalytic Activity of Phosphatases of Regenerating Liver in Early T Cell Receptor Signaling Dynamics and IL-2 Production |
title_sort | effect of pharmacological inhibition of the catalytic activity of phosphatases of regenerating liver in early t cell receptor signaling dynamics and il-2 production |
topic | Communication |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7177812/ https://www.ncbi.nlm.nih.gov/pubmed/32260565 http://dx.doi.org/10.3390/ijms21072530 |
work_keys_str_mv | AT aguilarsopenaoscar effectofpharmacologicalinhibitionofthecatalyticactivityofphosphatasesofregeneratingliverinearlytcellreceptorsignalingdynamicsandil2production AT hernandezperezsara effectofpharmacologicalinhibitionofthecatalyticactivityofphosphatasesofregeneratingliverinearlytcellreceptorsignalingdynamicsandil2production AT alegregomezsergio effectofpharmacologicalinhibitionofthecatalyticactivityofphosphatasesofregeneratingliverinearlytcellreceptorsignalingdynamicsandil2production AT castrosanchezpatricia effectofpharmacologicalinhibitionofthecatalyticactivityofphosphatasesofregeneratingliverinearlytcellreceptorsignalingdynamicsandil2production AT iglesiasceaceroalba effectofpharmacologicalinhibitionofthecatalyticactivityofphosphatasesofregeneratingliverinearlytcellreceptorsignalingdynamicsandil2production AT lazojohns effectofpharmacologicalinhibitionofthecatalyticactivityofphosphatasesofregeneratingliverinearlytcellreceptorsignalingdynamicsandil2production AT rodanavarropedro effectofpharmacologicalinhibitionofthecatalyticactivityofphosphatasesofregeneratingliverinearlytcellreceptorsignalingdynamicsandil2production |