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- W4313360095 abstract "Abstract Calcineurin is a phosphatase whose primary targets in T cells are NFAT transcription factors, and its inhibition with cyclosporin A (CsA) or FK506 is a cornerstone of immunosuppressive therapies. Here we show that calcineurin is recruited to the T cell receptor signaling complex where it reverses the inhibitory phosphorylation of Lck on Ser-59 (LckS59). Loss of calcineurin activity impaired phosphorylation of ZAP-70Y493 and some downstream pathways in a manner consistent with signaling in cells expressing LckS59A (non-phosphorylatable) or LckS59E (phosphomimetic). Importantly, CsA inhibited activation-induced LFA-1-dependent and NFAT-independent adhesion of T cells to ICAM-1, with little effect on cells expressing mutant Lck. These results provide a new understanding of how widely-used immunosuppressive drugs interfere with essential processes in the immune response." @default.
- W4313360095 created "2023-01-06" @default.
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- W4313360095 date "2017-05-01" @default.
- W4313360095 modified "2023-09-27" @default.
- W4313360095 title "Recruitment of calcineurin to the T cell receptor positively regulates T cell activation" @default.
- W4313360095 doi "https://doi.org/10.4049/jimmunol.198.supp.52.7" @default.
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