Protein tyrosine phosphatase SAP-1 protects against colitis through regulation of CEACAM20 in the intestinal epithelium

Murata Yoji; Kotani Takenori; Supriatna YanaKitamura YasuakiImada ShinyaKawahara KohichiNishio MikiDaniwijaya Edwin WidyantoSadakata HisanobuKusakari ShinyaMori MunemasaKanazawa YoshitakeSaito YasuyukiOkawa KatsuyaTakeda-Morishita MarikoOkazawa HidekiOhnishi HiroshiAzuma TakeshiSuzuki AkiraMatozaki Takashi

首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Protein tyrosine phosphatase SAP-1 protects against colitis through regulation of CEACAM20 in the intestinal epithelium

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Protein tyrosine phosphatase SAP-1 protects against colitis through regulation of CEACAM20 in the intestinal epithelium

机译：Protein tyrosine phosphatase SAP-1 protects against colitis through regulation of CEACAM20 in the intestinal epithelium

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Intestinal epithelial cells contribute to regulation of intestinal immunity in mammals, but the detailed molecular mechanisms of such regulation have remained largely unknown. Stomach-cancer-associated protein tyrosine phosphatase 1 (SAP-1, also known as PTPRH) is a receptor-type protein tyrosine phosphatase that is localized specifically at microvilli of the brush border in gastrointestinal epithelial cells. Here we show that SAP-1 ablation in interleukin (IL)-10-deficient mice, a model of inflammatory bowel disease, resulted in a marked increase in the severity of colitis in association with up-regulation of mRNAs for various cytokines and chemokines in the colon. Tyrosine phosphorylation of carcinoembryonic antigen-related cell adhesion molecule (CEACAM) 20, an intestinal microvillus-specific transmembrane protein of the Ig superfamily, was greatly increased in the intestinal epithelium of the SAP-1-deficient animals, suggesting that this protein is a substrate for SAP-1. Tyrosine phosphorylation of CEACAM20 by the protein tyrosine kinase c-Src and the consequent association of CEACAM20 with spleen tyrosine kinase (Syk) promoted the production of IL-8 in cultured cells through the activation of nuclear factor-kappa B (NF-kappa B). In addition, SAP-1 and CEACAM20 were found to form a complex through interaction of their ectodomains. SAP-1 and CEACAM20 thus constitute a regulatory system through which the intestinal epithelium contributes to intestinal immunity.

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《Proceedings of the National Academy of Sciences of the United States of America》 |2015年第31期|E4264-E4271|共8页
作者
Murata Yoji; Kotani Takenori; Supriatna YanaKitamura YasuakiImada ShinyaKawahara KohichiNishio MikiDaniwijaya Edwin WidyantoSadakata HisanobuKusakari ShinyaMori MunemasaKanazawa YoshitakeSaito YasuyukiOkawa KatsuyaTakeda-Morishita MarikoOkazawa HidekiOhnishi HiroshiAzuma TakeshiSuzuki AkiraMatozaki Takashi;
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作者单位

Kobe Univ, Grad Sch Med, Dept Biochem & Mol Biol, Div Mol & Cellular Signaling, Kobe, Hyogo 6500017, Japan;

Gunma Univ, Inst Mol & Cellular Regulat, Lab Biosignal Sci, Maebashi, Gunma 3718512, Japan;

Kyushu Univ, Med Inst Bioregulat, Div Canc Genet, Fukuoka 812, JapanKyowa Hakko Kirin Co, Drug Discovery Res Labs, Shizuoka 4118731, JapanKobe Gakuin Univ, Fac Pharmaceut Sci, Lab Drug Delivery Syst, Kobe, Hyogo 6508586, JapanGunma Univ, Grad Sch Hlth Sci, Dept Lab Sci, Maebashi, Gunma 3718514, Japan;

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收录信息美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
原文格式 PDF
正文语种英语
中图分类自然科学总论;
关键词
colitis; intestinal epithelial cells; intestinal immunity; protein tyrosine phosphatase;

Protein tyrosine phosphatase SAP-1 protects against colitis through regulation of CEACAM20 in the intestinal epithelium

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