SAP-1 is a microvillus-specific protein tyrosine phosphatase that modulates intestinal tumorigenesis.
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.
Sadakata
Hisanobu
H
Laboratory of Biosignal Sciences, Institute for Molecular and Cellular Regulation, Gunma University, 3-39-15 Showa-Machi, Maebashi, Gunma 371-8512, Japan.
Okazawa
Hideki
H
Sato
Takashi
T
Supriatna
Yana
Y
Ohnishi
Hiroshi
H
Kusakari
Shinya
S
Murata
Yoji
Y
Ito
Tomokazu
T
Nishiyama
Uichi
U
Minegishi
Takashi
T
Harada
Akihiro
A
Matozaki
Takashi
T
D000236:Adenoma / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D004848:Epithelium / Q000378:metabolism / Q000473:pathology; D017491:Genes, APC; D007414:Intestinal Neoplasms / Q000378:metabolism* / Q000473:pathology; D007421:Intestine, Small / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D008871:Microvilli / Q000378:metabolism*; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3 / Q000235:genetics / Q000378:metabolism*
D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3