Association of Intestinal Peptide Transport with a Protein Related to the Cadherin Superfamily

Abstract

The first step in oral absorption of many medically important peptide-based drugs is mediated by an intestinal proton-dependent peptide transporter. This transporter facilitates the oral absorption of beta-lactam antibiotics and angiotensin-converting enzyme inhibitors from the intestine into enterocytes lining the luminal wall. A monoclonal antibody that blocked uptake of cephalexin was used to identify and clone a gene that encodes an approximately 92-kilodalton membrane protein that was associated with the acquisition of peptide transport activity by transport-deficient cells. The amino acid sequence deduced from the complementary DNA sequence of the cloned gene indicated that this transport-associated protein shares several conserved structural elements with the cadherin superfamily of calcium-dependent, cell-cell adhesion proteins.

Cadherin-17 is a useful diagnostic marker for adenocarcinomas of the digestive system

“…Immunoreactivity of cytokeratin 7 was seen in adenocarcinomas from most body sites, which limits its clinical application. However, using cadherin-17/cytokeratin 7 two-marker profiles 6 were colorectal adenocarcinomas, and 1 was a prostatic adenocarcinoma. Hence, the cadherin-17/cytokeratin 7 profile can differentiate adenocarcinoma of upper and lower GI tract with high specificity.…”

“…5,6 Unlike the so-called classic cadherins, such as E-, N-, and P-cadherins, cadherin-17 has seven cadherin repeats instead of five within the extracellular domain and only 20 amino-acid residues in the cytoplasmic domain. The markedly short cytoplasmic domain lacks homology with other cadherins and the adhesive function of cadherin-17 is not dependent on association with other cytoplasmic proteins.…”

Cloning and functional characterisation of a peptide transporter expressed in the scutellum of barley grain during the early stages of germination

“…Included in this subfamily are CHL1, RCH2, HvPTR1 and a putative peptide transporter expressed in the root nodules of Lotus japonicus (LjNOD65, Szczyglowski et al, 1997). Eukaryotic peptide transporters that display no significant amino acid sequence similarity to the PTR transporter family have been cloned from the human intestine (Hpt-1, Dantzig et al, 1994) and Candida albicans (Opt-1p, Lubkowitz et al, 1997) and are excluded from Figure 4.…”

Uptake and transport of a novel anticancer drug-delivery system: lactosyl-norcantharidin-associated N-trimethyl chitosan nanoparticles across intestinal Caco-2 cell monolayers

“…Among these transporters, some promote drug absorption. 19 However, others (P-gp, MRP2, and MRP1) are known to restrict drug absorption in the intestinal mucosa. 20 In the uptake study, concentration dependence or saturation was observed for the uptake of Lac-NCTD in the concentration range of 100 µg/mL to 400 µg/mL.…”