https://scholars.lib.ntu.edu.tw/handle/123456789/540677
標題: | Syk is involved in NLRP3 inflammasome-mediated caspase-1 activation through adaptor ASC phosphorylation and enhanced oligomerization | 作者: | Lin Y.-C. Huang D.-Y. Wang J.-S. Lin Y.-L. Hsieh S.-L. KUO-CHIN HUANG WAN-WAN LIN |
公開日期: | 2015 | 出版社: | Federation of American Societies for Experimental Biology | 卷: | 97 | 期: | 5 | 起(迄)頁: | 825-835 | 來源出版物: | Journal of Leukocyte Biology | 摘要: | NLRP3 is the most crucial member of the NLR family, as it detects the existence of pathogen invasion and selfderived molecules associated with cellular damage. Several studies have reported that excessive NLRP3 inflammasome-mediated caspase-1 activation is a key factor in the development of diseases. Recent studies have reported that Syk is involved in pathogen-induced NLRP3 inflammasome activation; however, the detailed mechanism linking Syk to NLRP3 inflammasome remains unclear. In this study, we showed that Syk mediates NLRP3 stimuli-induced processing of procaspase-1 and the consequent activation of caspase-1. Moreover, the kinase activity of Syk is required to potentiate caspase-1 activation in a reconstituted NLRP3 inflammasome system in HEK293T cells. The adaptor protein ASC bridges NLRP3 with the effector protein caspase-1. Herein, we find that Syk can associate directly with ASC and NLRP3 by its kinase domain but interact indirectly with procaspase-1. Syk can phosphorylate ASC at Y146 and Y187 residues, and the phosphorylation of both residues is critical to enhance ASC oligomerization and the recruitment of procaspase-1. Together, our results reveal a new molecular pathway through which Syk promotes NLRP3 inflammasome formation, resulting from the phosphorylation of ASC. Thus, the control of Syk activity might be effective to modulate NLRP3 inflammasome activation and treat NLRP3-related immune diseases. ? Society for Leukocyte Biology. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84929166798&doi=10.1189%2fjlb.3HI0814-371RR&partnerID=40&md5=2f473c9b077abe83590cd504970c56c6 https://scholars.lib.ntu.edu.tw/handle/123456789/540677 |
ISSN: | 0741-5400 | DOI: | 10.1189/jlb.3HI0814-371RR | SDG/關鍵字: | adaptor protein; ASC protein; cryopyrin; inflammasome; interleukin 1beta converting enzyme; protein kinase Syk; unclassified drug; animal experiment; Article; controlled study; enzyme activation; enzyme activity; gene expression; human; human cell; macrophage; mouse; nonhuman; oligomerization; priority journal; protein phosphorylation; protein processing; site directed mutagenesis |
顯示於: | 醫學系 |
在 IR 系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。