T cell receptor stimulation impairs IL-7 receptor signaling by inducing expression of the microRNA miR-17 to target Janus kinase 1.

TitleT cell receptor stimulation impairs IL-7 receptor signaling by inducing expression of the microRNA miR-17 to target Janus kinase 1.
Publication TypeJournal Article
Year of Publication2014
AuthorsKatz G, Pobezinsky LA, Jeurling S, Shinzawa M, Van Laethem F, Singer A
JournalSci Signal
Volume7
Issue340
Paginationra83
Date Published2014
ISSN1937-9145
Abstract

T cell receptor (TCR)-mediated inhibition of interleukin-7 (IL-7) signaling is important for lineage fate determination in the thymus and for T cell survival in the periphery because uninterrupted IL-7 signaling results in T cell death. The initial event in IL-7 signaling is the transactivation of Janus kinases 1 and 3 (Jak1 and Jak3), which are associated with the cytosolic tails of the IL-7 receptor α chain (IL-7Rα) and the γc subunit, the two cell surface proteins that constitute IL-7R. We found that Jak1 is a highly unstable protein with a half-life of only 1.5 hours, so that continuous Jak1 protein synthesis is required to maintain Jak1 protein in sufficient abundance to support IL-7 signaling. However, we also found that Jak1 protein synthesis was acutely reduced by TCR-responsive microRNAs in the miR-17 family, which targeted Jak1 mRNA (messenger RNA) to inhibit its translation. Thus, this study identifies a molecular mechanism by which TCR engagement acutely disrupts IL-7 signaling.

DOI10.1126/scisignal.2005221
Alternate JournalSci Signal
PubMed ID25161318