SAP-1 is a microvillus-specific protein tyrosine phosphatase that modulates intestinal tumorigenesis

SAP-1 is a microvillus-specific protein tyrosine phosphatase that modulates intestinal tumorigenesis
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DOI:
10.1111/j.1365-2443.2008.01270.x
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发表时间:
2009-03-01
期刊:
影响因子:
2.1
通讯作者:
Matozaki, Takashi
Matozaki, Takashi
中科院分区:
生物学4区
文献类型:
--
作者:
Sadakata, Hisanobu;Okazawa, Hideki;Matozaki, Takashi

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SAP-1(PTPRH)是一种受体型蛋白酪氨酸磷酸酶(RPTP),其胞内区为单一催化结构域,胞外区为纤维连接蛋白III型结构域。然而,这种RPTP的细胞定位和生物学功能仍不清楚。我们现在发现,小鼠SAP-1mRNA主要局限于胃肠道,SAP-1蛋白定位于胃肠道上皮细胞刷状边缘的微绒毛。SAP-1在小鼠肠道中的表达在胚胎发育过程中很少,但在出生后显着增加。SAP-1基因缺陷小鼠的肠上皮形态无明显变化。相反,切除SAP-1抑制了携带腺瘤性息肉病基因杂合突变的小鼠的肿瘤形成。这些结果表明SAP-1是一种微绒毛特异性RPTP,调节肠道肿瘤的发生。
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.