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IL-13Rα2 uses TMEM219 in chitinase 3-like-1-induced signalling and effector responses

Author

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  • Chang-Min Lee

    (Brown University)

  • Chuan Hua He

    (Brown University)

  • Adel M. Nour

    (Brown University)

  • Yang Zhou

    (Brown University)

  • Bing Ma

    (Brown University)

  • Jin Wook Park

    (Brown University)

  • Kyung Hee Kim

    (Emory University School of Medicine)

  • Charles Dela Cruz

    (Section of Pulmonary and Critical Care and Sleep Medicine, Yale University School of Medicine)

  • Lokesh Sharma

    (Section of Pulmonary and Critical Care and Sleep Medicine, Yale University School of Medicine)

  • Mahmoud L. Nasr

    (Harvard Medical School)

  • Yorgo Modis

    (Harvard Medical School)

  • Chun Geun Lee

    (Brown University)

  • Jack A. Elias

    (Brown University
    Warren Alpert School of Medicine, Brown University)

Abstract

Recent studies demonstrated that chitinase 3-like-1 (Chi3l1) binds to and signals via IL-13Rα2. However, the mechanism that IL-13Rα2 uses to mediate the effects of Chi3l1 has not been defined. Here, we demonstrate that the membrane protein, TMEM219, is a binding partner of IL-13Rα2 using yeast two-hybrid, co-immunoprecipitation, co-localization and bimolecular fluorescence complementation assays. Furthermore, fluorescence anisotropy nanodisc assays revealed a direct physical interaction between TMEM219 and IL-13Rα2-Chi3l1 complexes. Null mutations or siRNA silencing of TMEM219 or IL-13Rα2 similarly decreased Chi3l1-stimulated epithelial cell HB-EGF production and macrophage MAPK/Erk and PKB/Akt activation. Null mutations of TMEM219 or IL-13Rα2 also phenocopied one another as regards the ability of Chi3l1 to inhibit oxidant-induced apoptosis and lung injury, promote melanoma metastasis and stimulate TGF-β1. TMEM219 also contributed to the decoy function of IL-13Rα2. These studies demonstrate that TMEM219 plays a critical role in Chi3l1-induced IL-13Rα2 mediated signalling and tissue responses.

Suggested Citation

  • Chang-Min Lee & Chuan Hua He & Adel M. Nour & Yang Zhou & Bing Ma & Jin Wook Park & Kyung Hee Kim & Charles Dela Cruz & Lokesh Sharma & Mahmoud L. Nasr & Yorgo Modis & Chun Geun Lee & Jack A. Elias, 2016. "IL-13Rα2 uses TMEM219 in chitinase 3-like-1-induced signalling and effector responses," Nature Communications, Nature, vol. 7(1), pages 1-13, November.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms12752
    DOI: 10.1038/ncomms12752
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