| First Author | Lee CM | Year | 2016 |
| Journal | Nat Commun | Volume | 7 |
| Pages | 12752 | PubMed ID | 27629921 |
| Mgi Jnum | J:236976 | Mgi Id | MGI:5810479 |
| Doi | 10.1038/ncomms12752 | Citation | Lee CM, et al. (2016) IL-13Ralpha2 uses TMEM219 in chitinase 3-like-1-induced signalling and effector responses. Nat Commun 7:12752 |
| abstractText | Recent studies demonstrated that chitinase 3-like-1 (Chi3l1) binds to and signals via IL-13Ralpha2. However, the mechanism that IL-13Ralpha2 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-13Ralpha2 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-13Ralpha2-Chi3l1 complexes. Null mutations or siRNA silencing of TMEM219 or IL-13Ralpha2 similarly decreased Chi3l1-stimulated epithelial cell HB-EGF production and macrophage MAPK/Erk and PKB/Akt activation. Null mutations of TMEM219 or IL-13Ralpha2 also phenocopied one another as regards the ability of Chi3l1 to inhibit oxidant-induced apoptosis and lung injury, promote melanoma metastasis and stimulate TGF-beta1. TMEM219 also contributed to the decoy function of IL-13Ralpha2. These studies demonstrate that TMEM219 plays a critical role in Chi3l1-induced IL-13Ralpha2 mediated signalling and tissue responses. |
