title: IL-13Rα2 uses TMEM219 in chitinase 3-like-1-induced signalling and effector responses.
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.
authors.affiliation: Department of Molecular Microbiology and Immunology, Brown University, 185 Meeting Street, Box G-L, Providence, Rhode Island 02912, USA.
authors.forename: Chang-Min
authors.initials: CM
authors.lastname: Lee
authors.affiliation: Department of Molecular Microbiology and Immunology, Brown University, 185 Meeting Street, Box G-L, Providence, Rhode Island 02912, USA.
authors.forename: Chuan Hua
authors.initials: CH
authors.lastname: He
authors.affiliation: Department of Molecular Microbiology and Immunology, Brown University, 185 Meeting Street, Box G-L, Providence, Rhode Island 02912, USA.
authors.forename: Adel M
authors.initials: AM
authors.lastname: Nour
authors.affiliation: Department of Molecular Microbiology and Immunology, Brown University, 185 Meeting Street, Box G-L, Providence, Rhode Island 02912, USA.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Molecular Microbiology and Immunology, Brown University, 185 Meeting Street, Box G-L, Providence, Rhode Island 02912, USA.
authors.forename: Bing
authors.initials: B
authors.lastname: Ma
authors.affiliation: Department of Molecular Microbiology and Immunology, Brown University, 185 Meeting Street, Box G-L, Providence, Rhode Island 02912, USA.
authors.forename: Jin Wook
authors.initials: JW
authors.lastname: Park
authors.affiliation: Division of Cardiology, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
authors.forename: Kyung Hee
authors.initials: KH
authors.lastname: Kim
authors.affiliation: Section of Pulmonary and Critical Care and Sleep Medicine, Department of Medicine, Yale University School of Medicine, 300 Cedar Street, New Haven, Connecticut 06520, USA.
authors.forename: Charles
authors.initials: C
authors.lastname: Dela Cruz
authors.affiliation: Section of Pulmonary and Critical Care and Sleep Medicine, Department of Medicine, Yale University School of Medicine, 300 Cedar Street, New Haven, Connecticut 06520, USA.
authors.forename: Lokesh
authors.initials: L
authors.lastname: Sharma
authors.affiliation: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 240 Longwood Avenue, Boston, Massachusetts 02115, USA.
authors.forename: Mahmoud L
authors.initials: ML
authors.lastname: Nasr
authors.affiliation: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 240 Longwood Avenue, Boston, Massachusetts 02115, USA.
authors.forename: Yorgo
authors.identifier: 0000-0002-6084-0429
authors.initials: Y
authors.lastname: Modis
authors.affiliation: Department of Molecular Microbiology and Immunology, Brown University, 185 Meeting Street, Box G-L, Providence, Rhode Island 02912, USA.
authors.forename: Chun Geun
authors.identifier: 0000-0002-9514-3658
authors.initials: CG
authors.lastname: Lee
authors.affiliation: Department of Molecular Microbiology and Immunology, Brown University, 185 Meeting Street, Box G-L, Providence, Rhode Island 02912, USA.|Division of Medicine and Biological Sciences, Warren Alpert School of Medicine, Brown University, Box G-A1, 97 Waterman Street, Providence, Rhode Island 02912, USA.
authors.forename: Jack A
authors.initials: JA
authors.lastname: Elias
mesh_terms: D000818:Animals; D017209:Apoptosis; D045744:Cell Line, Tumor; D000071451:Chitinase-3-Like Protein 1 / Q000378:metabolism*; D066257:Heparin-binding EGF-like Growth Factor / Q000378:metabolism; D006801:Humans; D053663:Interleukin-13 Receptor alpha2 Subunit / Q000378:metabolism*; D055370:Lung Injury / Q000378:metabolism; D008175:Lung Neoplasms / Q000378:metabolism / Q000556:secondary; D020935:MAP Kinase Signaling System; D008546:Melanoma, Experimental / Q000378:metabolism / Q000473:pathology; D008565:Membrane Proteins / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D009362:Neoplasm Metastasis; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D020798:Two-Hybrid System Techniques; D060449:Wnt Signaling Pathway
chemical_list: C084533:CHI3L1 protein, human; D000071451:Chitinase-3-Like Protein 1; D066257:Heparin-binding EGF-like Growth Factor; D053663:Interleukin-13 Receptor alpha2 Subunit; D008565:Membrane Proteins; C000628132:TMEM219 protein, human; C508961:Tgfb1 protein, mouse; C000628133:Tmem219 protein, mouse; D053773:Transforming Growth Factor beta1; D051057:Proto-Oncogene Proteins c-akt