IL‐37‐induced activation of glycogen synthase kinase 3β promotes IL‐1R8/Sigirr phosphorylation, internalization, and degradation in lung epithelial cells
| العنوان: | IL‐37‐induced activation of glycogen synthase kinase 3β promotes IL‐1R8/Sigirr phosphorylation, internalization, and degradation in lung epithelial cells |
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| المؤلفون: | Lian Li, Tomeka Suber, Sarah J Taleb, Qinmao Ye, Jiaxing Miao, Shuang Li, Arya S. Tamaskar, Kevin C Tran, Jing Zhao, Jianxin Wei, Yutong Zhao |
| المصدر: | J Cell Physiol |
| بيانات النشر: | Wiley, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 0301 basic medicine, Proteasome Endopeptidase Complex, Physiology, media_common.quotation_subject, Clinical Biochemistry, Article, Mice, 03 medical and health sciences, 0302 clinical medicine, Ubiquitin, GSK-3, Animals, Humans, Phosphorylation, Receptor, Internalization, Glycogen synthase, Lung, Cells, Cultured, media_common, Toll-like receptor, Glycogen Synthase Kinase 3 beta, biology, Kinase, Chemistry, Toll-Like Receptors, Receptors, Interleukin-1, Epithelial Cells, Cell Biology, Cell biology, 030104 developmental biology, 030220 oncology & carcinogenesis, biology.protein, Interleukin-1, Signal Transduction |
| الوصف: | Interleukin (IL)-37 diminishes a variety of inflammatory responses through ligation to its receptor IL-1R8/Sigirr. Sigirr is a Toll like receptor (TLR)/IL-1R family member. We have shown that Sigirr is not stable in response to IL-37 treatment, IL-37-induced Sigirr degradation is mediated by the ubiquitin-proteasome system, and that the process is reversed by a deubiquitinase, USP13. However, the molecular mechanisms by which USP13 regulates Sigirr stability have not been revealed. In this study, we investigate the roles of glycogen synthesis kinase 3β (GSK3β) in Sigirr phosphorylation and stability. IL-37 stimulation induced Sigirr phosphorylation and degradation, as well as activation of GSK3β. Inhibition of GSK3β attenuated IL-37-induced Sigirr phosphorylation, while exogenous expressed GSK3β promoted Sigirr phosphorylation at threonine (T)372 residue. Sigirr association with GSK3β was detected. Amino acid residues 51–101 in GSK3β were identified as the Sigirr binding domain. These data indicate that GSK3β mediates IL-37-induced threonine phosphorylation of Sigirr. Further, we investigated the role of GSK3β-mediated phosphorylation of Sigirr in Sigirr degradation. Inhibition of GSK3β attenuated IL-37-induced Sigirr degradation, while T372 mutant of Sigirr was resistant to IL-37-mediated degradation. Furthermore, inhibition of Sigirr phosphorylation prevented Sigirr internalization and association with USP13, suggesting GSK3β promotes Sigirr degradation through disrupting Sigirr association with USP13. |
| تدمد: | 1097-4652 0021-9541 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::93a4f02ef08482c0122ce48d63df0ec4 https://doi.org/10.1002/jcp.30253 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....93a4f02ef08482c0122ce48d63df0ec4 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10974652 00219541 |
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