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

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.

Shear Stress-induced Redistribution of Vascular Endothelial-Protein-tyrosine Phosphatase (VE-PTP) in Endothelial Cells and Its Role in Cell Elongation

“…Plasmids-Expression vectors for mouse VE-PTP, SAP-1, or PTPRO were generated as described previously (12,17,18). For construction of an expression vector for the ⌬cyto mutant of VE-PTP, which lacks most of the cytoplasmic region of the protein, a DNA fragment corresponding to amino acids 1-1645 of mouse VE-PTP was amplified by PCR and subcloned into pEntr-CMV (12).…”

“…Antibodies and Reagents-A rat mAb and rabbit polyclonal antibodies (pAbs) to VE-PTP (12) as well as rat mAbs to SAP-1 and to PTPRO (17,18) were described previously. Mouse mAbs to the HA epitope tag (12CA5) and to ␤-tubulin were obtained from Roche Applied Science and Sigma, respectively.…”

Substrate Specificity of R3 Receptor-like Protein-tyrosine Phosphatase Subfamily toward Receptor Protein-tyrosine Kinases

“…On the other hand, inactivation of EphB2 has been shown to accelerate tumorigenesis in the colon and rectum in heterozygous adenomatous polyposis coli (APC) mutant mice (34). Interestingly, Ptprh deficiency suppresses intestinal tumorigenesis in a heterozygous APC mutant background through an unknown mechanism (25). Here, Ptprh presumably inhibits the tumor suppressor function of EphB2 in the intestine.…”

“…Ptprj is broadly expressed in various cell types, including endothelial, epithelial, hematopoietic, and neuronal cells (24). On the other hand, expression of Ptprh is restricted to the gastrointestinal tract, and its protein product localizes to the microvilli of gastrointestinal epithelial cells (25). According to the data of Gene Expression Omnibus (GEO, NCBI), all of the RPTKs identified as substrate candidates are expected to be coexpressed with the corresponding R3 RPTPs.…”

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

“…It was previously shown to be localized specifically to microvilli of the brush border in epithelial cells of the small intestine and stomach in mice (18). SAP-1-deficient mice manifest no marked changes in the morphology of the small intestinal epithelium (18), suggesting that SAP-1 is not important for determination of the cellular architecture of this tissue. Moreover, SAP-1 is dispensable for regulation of food digestion and absorption of nutrients and electrolytes in the intestine.…”