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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2016-09-15

AUTHORS

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

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. More... »

PAGES

12752

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/ncomms12752

DOI

http://dx.doi.org/10.1038/ncomms12752

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1021052788

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/27629921


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