Chitinase 3-like-1-tmem219-interleukin-13 receptor-ligand alpha-2 signalling complex
Components
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protein -
IL13 (unspecified role)
Interleukin-13
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protein -
TMEM219 (unspecified role)
Insulin-like growth factor-binding protein 3 receptor
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protein -
IL13RA2 (unspecified role)
Interleukin-13 receptor subunit alpha-2
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protein -
CHI3L1 (unspecified role)
Chitinase-3-like protein 1
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Function
Complex formed upon Chitinase-3-like protein 1 (CHI3L1) binding to interleukin-13 receptor alpha-2 (IL13RA2) by associating with TMEM219 which is a cell-death receptor for IGFBP-3 (P17936). CHI3L1 interaction with IL13RA2 through a TMEM219-dependent pathway prevents cell death by activating the MAP kinases, ERK1/2 and AKT pathways, while direct interaction with IL13RA2 results in apoptosis through activation of Wnt/beta-catenin (P35222). Functional effects of this complex is also moderated by LGALS3 (P17931), which physically interacts with IL13RA2 and CHI3L1 to compete with TMEM219 for IL13RA2 binding, thereby diminishing the anti-apoptotic role of CHI3L1. IL13RA2 also forms a complex with IL13 and TMEM219 (CPX847) which largely acts as a decoy to diminish IL13 activity. IL13RA2 N-glycosylation is a critical determinant of whether it binds CHI3L1 or IL13; CHI3L1 binding to IL13RA2 and signalling is increased if IL13RA2 N-glycosylation is diminished. CHI3L1 is a carbohydrate-binding lectin with a preference for chitin, produced by immune cells, osteoclasts, chondrocytes, smooth muscle cells, astrocytes and cancer cells upon stimulation from several interleukins including IL13, IL6, IL1B and TNF. CHI3L1 expression is inhibited by miR-24, miR-342-3p, miR-449a, miR125a-3p and miR-96-5p. CHI3L1 binding to IL13RA2 leads to inflammasome activation, melanoma metastasis, apoptosis, oxidative damage, allergic inflammation, wound healing, fibrosis, and TGFB1 production. CH3L1 also plays a key role in antipathogenic responses and is involved in stimulating disease tolerance by controlling cell death, inflammation and remodelling.
GO - Molecular Function (1)
cytokine receptor activity |
GO - Biological Process (3)
apoptotic process |
transforming growth factor beta1 production |
ERK1 and ERK2 cascade |
Properties
Additional Information
Further Reading
Identifier | Title | Author(s) |
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27629921 | IL-13Rα2 uses TMEM219 in chitinase 3-like-1-induced signalling and effector responses. | Lee CM, He CH, Nour AM, Zhou Y, Ma B, Park JW, Kim KH, Dela Cruz C, Sharma L, Nasr ML, Modis Y, Lee CG, Elias JA. |
32402213 | <i>N</i>-Glycosylation Regulates Chitinase 3-like-1 and IL-13 Ligand Binding to IL-13 Receptor α2. | He CH, Lee CG, Ma B, Kamle S, Choi AMK, Elias JA. |
36152905 | Interleukin 13 receptor alpha 2 (IL13Rα2): Expression, signaling pathways and therapeutic applications in cancer. | Jaén M, Martín-Regalado Á, Bartolomé RA, Robles J, Casal JI. |
32929074 | Chitinase-3 like-protein-1 function and its role in diseases. | Zhao T, Su Z, Li Y, Zhang X, You Q. |
23972995 | Chitinase 3-like 1 regulates cellular and tissue responses via IL-13 receptor α2. | He CH, Lee CG, Dela Cruz CS, Lee CM, Zhou Y, Ahangari F, Ma B, Herzog EL, Rosenberg SA, Li Y, Nour AM, Parikh CR, Schmidt I, Modis Y, Cantley L, Elias JA. |
38177294 | Significance of chitinase-3-like protein 1 in the pathogenesis of inflammatory diseases and cancer. | Yu JE, Yeo IJ, Han SB, Yun J, Kim B, Yong YJ, Lim YS, Kim TH, Son DJ, Hong JT. |
Synonyms (2)
YKL40-IGFBP-3R-IL13-IL13RA2 complex |
BRP-39-TMEM219-IL13-IL13RA2 complex |
Systematic Name
TMEM219:CHI3L1:IL13:IL13RA2 |