Journal
NATURE COMMUNICATIONS
Volume 7, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms12752
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Funding
- NIH [R01 HL093017, U01 HL108638, R01 HL115813]
- Korea Drug Development Fund (KDDF) [KDDF-20132-11]
- Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Education of Korea [NRF-2012R1A6A3A03040533]
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Recent studies demonstrated that chitinase 3-like-1 (Chi3l1) binds to and signals via IL-13R alpha 2. However, the mechanism that IL-13R alpha 2 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-13R alpha 2 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-13R alpha 2-Chi3l1 complexes. Null mutations or siRNA silencing of TMEM219 or IL-13R alpha 2 similarly decreased Chi3l1-stimulated epithelial cell HB-EGF production and macrophage MAPK/Erk and PKB/Akt activation. Null mutations of TMEM219 or IL-13R alpha 2 also phenocopied one another as regards the ability of Chi3l1 to inhibit oxidant-induced apoptosis and lung injury, promote melanoma metastasis and stimulate TGF-beta 1. TMEM219 also contributed to the decoy function of IL-13R alpha 2. These studies demonstrate that TMEM219 plays a critical role in Chi3l1-induced IL-13R alpha 2 mediated signalling and tissue responses.
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