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Sci. Signal., 24 February 2009
Vol. 2, Issue 59, p. ra8
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-B, C/EBP, and C/EBPβ. Although IL-17RA–mediated activation of NF-B and C/EBP 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).
Caini Liu, Shadi Swaidani, Wen Qian, Zizhen Kang, Paige Sun, Yue Han, Chenhui Wang, Muhammet Fatih Gulen, Weiguo Yin, Chunjiang Zhang, Paul L. Fox, Mark Aronica, Thomas A. Hamilton, Saurav Misra, Junpeng Deng, and Xiaoxia Li (1 November 2011) Sci. Signal.4 (197), ra72.
[DOI: 10.1126/scisignal.2001843] |Editor's Summary »|Abstract »|Full Text »|PDF »|Supplementary Materials »