| First Author | Katz G | Year | 2014 |
| Journal | Sci Signal | Volume | 7 |
| Issue | 340 | Pages | ra83 |
| PubMed ID | 25161318 | Mgi Jnum | J:260393 |
| Mgi Id | MGI:6141583 | Doi | 10.1126/scisignal.2005221 |
| Citation | Katz G, et al. (2014) T cell receptor stimulation impairs IL-7 receptor signaling by inducing expression of the microRNA miR-17 to target Janus kinase 1. Sci Signal 7(340):ra83 |
| abstractText | 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 alpha chain (IL-7Ralpha) and the gammac 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. |
