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SAP-1 is a microvillus-specific protein tyrosine phosphatase that modulates intestinal tumorigenesis |
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| Authors: | Hisanobu Sadakata Hideki Okazawa Takashi Sato Yana Supriatna Hiroshi Ohnishi Shinya Kusakari Yoji Murata Tomokazu Ito Uichi Nishiyama Takashi Minegishi Akihiro Harada Takashi Matozaki |
| Institution: | Laboratory of Biosignal Sciences, Institute for Molecular and Cellular Regulation, Gunma University, 3-39-15 Showa-Machi, Maebashi, Gunma 371-8512, Japan; Department of Obstetrics and;Gynecology, Graduate School of Medicine, Gunma University, 3-39-22 Showa-Machi, Maebashi, Gunma 371-8511, Japan Laboratory of Molecular Traffic, Institute for Molecular and Cellular Regulation, Gunma University, 3-39-15 Showa-Machi, Maebashi, Gunma 371-8512, Japan; Pharmaceutical Development Laboratories, Kirin Brewery Co. Ltd., Takasaki, Gunma 370-1295, Japan |
| Abstract: | SAP-1 (PTPRH) is a receptor-type protein tyrosine phosphatase (RPTP) with a single catalytic domain in its cytoplasmic region and fibronectin type III-like domains in its extracellular region. The cellular localization and biological functions of this RPTP have remained unknown, however. We now show that mouse SAP-1 mRNA is largely restricted to the gastrointestinal tract and that SAP-1 protein localizes to the microvilli of the brush border in gastrointestinal epithelial cells. The expression of SAP-1 in mouse intestine is minimal during embryonic development but increases markedly after birth. SAP-1-deficient mice manifested no marked changes in morphology of the intestinal epithelium. In contrast, SAP-1 ablation inhibited tumorigenesis in mice with a heterozygous mutation of the adenomatous polyposis coli gene. These results thus suggest that SAP-1 is a microvillus-specific RPTP that regulates intestinal tumorigenesis. |
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