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

RESEARCH ARTICLES

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).

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