The regulatory role of most dual specific phosphatases during T cell activation remains unknown. Here, we have studied the expression and function of phosphatases of regenerating liver (PRLs: PRL-1, PRL-2, and PRL-3) during T cell activation, as well as, the dynamic delivery of PRL-1 to the Immunological Synapse (IS). We found that T cell activation downregulates the expression of PRL-2, resulting in an increased PRL-1/PRL-2 ratio. PRL-1 redistributed at the IS in two stages: Initially, it was transiently accumulated at scanning membranes enriched in CD3 and actin, and at later times, it was delivered at the contact site from pericentriolar, CD3∂-containing, vesicles. Once at the established IS, PRL-1 distributed to LFA-1 and CD3ϵ sites. Remarkably, PRL-1 was found to regulate actin dynamics during IS assembly and the secretion of IL-2. Moreover, pharmacological inhibition of the catalytic activity of the three PRLs reduced the secretion of IL-2. These results provide evidence indicating a regulatory role of PRL-1 during IS assembly and highlight the involvement of PRLs in immune responses by mature T cells.
CITATION STYLE
Castro-Sánchez, P., Ramirez-Munoz, R., Martín-Cófreces, N. B., Aguilar-Sopeña, O., Alegre-Gomez, S., Hernández-Pérez, S., … Roda-Navarro, P. (2018). Phosphatase of regenerating liver-1 (PRL-1) regulates actin dynamics during immunological synapse assembly and t cell effector function. Frontiers in Immunology, 9(NOV). https://doi.org/10.3389/fimmu.2018.02655
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