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

Genes Cells. 2009 Mar;14(3):295-308. doi: 10.1111/j.1365-2443.2008.01270.x. Epub 2009 Jan 12.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoma / metabolism*
  • Adenoma / pathology
  • Animals
  • Epithelium / metabolism
  • Epithelium / pathology
  • Genes, APC
  • Intestinal Neoplasms / metabolism*
  • Intestinal Neoplasms / pathology
  • Intestine, Small / metabolism*
  • Intestine, Small / pathology
  • Mice
  • Mice, Knockout
  • Microvilli / metabolism*
  • Receptor-Like Protein Tyrosine Phosphatases, Class 3 / genetics
  • Receptor-Like Protein Tyrosine Phosphatases, Class 3 / metabolism*

Substances

  • Receptor-Like Protein Tyrosine Phosphatases, Class 3