Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Sci. Signal., 24 February 2009
Vol. 2, Issue 59, p. ra8
[DOI: 10.1126/scisignal.2000066]

RESEARCH

Editor's Summary

Getting Negative
Interleukin 17 (IL-17) is a proinflammatory cytokine that is important in mediating immune responses to infectious organisms. In addition, IL-17 plays a critical role in the pathology of autoimmune disorders. Recently, an IL-17–secreting population of T cells, termed T helper 17 (TH17), has been identified as a distinct T cell lineage, stimulating interest in the properties of these cells and the signaling mechanisms of IL-17. IL-17 signals through a receptor complex consisting of IL-17RA and IL-17RC subunits, which have several structural features that distinguish them from other cytokine receptors. Signaling through IL-17RA leads to the activation of the transcription factors NF-{kappa}B, C/EBP{delta}, and C/EBPβ. Although IL-17RA–mediated activation of NF-{kappa}B and C/EBP{delta} is well understood, how IL-17 regulates the activity of C/EBPβ is unclear. Shen et al. used tandem mass spectrometry and other experiments to show that IL-17RA signaling led to the sequential, dual phosphorylation of C/EBPβ. Whereas the first phosphorylation event depended on the activity of extracellular signal–regulated kinase, the second depended on that of glycogen synthase kinase 3β. Phosphorylation of C/EBPβ resulted in repressed expression of IL-17 target genes, the first characterized negative consequence of IL-17R signaling.

Citation: F. Shen, N. Li, P. Gade, D. V. Kalvakolanu, T. Weibley, B. Doble, J. R. Woodgett, T. D. Wood, S. L. Gaffen, IL-17 Receptor Signaling Inhibits C/EBPβ by Sequential Phosphorylation of the Regulatory 2 Domain. Sci. Signal. 2, ra8 (2009).

Read the Full Text

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Act1, a U-box E3 Ubiquitin Ligase for IL-17 Signaling.
C. Liu, W. Qian, Y. Qian, N. V. Giltiay, Y. Lu, S. Swaidani, S. Misra, L. Deng, Z. J. Chen, and X. Li (2009)
Science Signaling 2, ra63
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882