Association of intestinal peptide transport with a protein related to the cadherin superfamily.
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.
Dantzig
A H
AH
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285.
Hoskins
J A
JA
Tabas
L B
LB
Bright
S
S
Shepard
R L
RL
Jenkins
I L
IL
Duckworth
D C
DC
Sportsman
J R
JR
Mackensen
D
D
Rosteck
P R
PR
D000595:Amino Acid Sequence; D000818:Animals; D001692:Biological Transport; D016466:CHO Cells; D015820:Cadherins / Q000737:chemistry*; D002352:Carrier Proteins / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D002506:Cephalexin / Q000378:metabolism*; D003001:Cloning, Molecular; D006224:Cricetinae; D006031:Glycosylation; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007413:Intestinal Mucosa / Q000378:metabolism*; D007930:Leucine / Q000031:analogs & derivatives / Q000378:metabolism; D026901:Membrane Transport Proteins; D051379:Mice; D008805:Mice, Inbred A; D008969:Molecular Sequence Data; D016366:Open Reading Frames; D017386:Sequence Homology, Amino Acid; D014162:Transfection; D014407:Tumor Cells, Cultured
C490584:CDH17 protein, human; D015820:Cadherins; D002352:Carrier Proteins; C490585:Cdh17 protein, mouse; D026901:Membrane Transport Proteins; C067802:intestinal peptide-proton cotransporter; D007930:Leucine; C012211:ubenimex; D002506:Cephalexin