Journal
BIOCHEMICAL JOURNAL
Volume 438, Issue -, Pages 71-80Publisher
PORTLAND PRESS LTD
DOI: 10.1042/BJ20110111
Keywords
aldo-keto reductase family 1; member B10 (AKR1B10); ATP-binding-cassette transporter (ABC transporter); calcium signalling; cancer marker; lysosomal exocytosis; non-classical protein-secretion pathway
Categories
Funding
- National Cancer Institute [CA122622]
- Department of Defense [BC083555]
Ask authors/readers for more resources
AKR1B10 (aldo-keto reductase family 1, member B10) protein is primarily expressed in normal human small intestine and colon, but overexpressed in several types of human cancers and considered as a tumour marker. In the present study, we found that AKR1B10 protein is secreted from normal intestinal epithelium and cultured cancer cells, as detected by a newly developed sandwich ELISA and Western blotting. The secretion of AKR1B10 was not affected by the protein-synthesis inhibitor cycloheximide and the classical protein-secretion pathway inhibitor brefeldin A, but was stimulated by temperature, ATP, Ca(2+) and the Ca(2+) carrier ionomycin, lysosomotropic NH(4)Cl, the G-protein activator GTP gamma S and the G-protein coupling receptor N-formylmethionyl-leucyl-phenylalanine. The ADP-ribosylation factor inhibitor 2-(4-fluorobenzoylamino)-benzoic acid methyl ester and the phospholipase C inhibitor U73122 inhibited the secretion of AKR1B10. In cultured cells, AKR1B10 was present in lysosomes and was secreted with cathepsin D, a lysosomal marker. In the intestine, AKR1B10 was specifically expressed in mature epithelial cells and secreted into the lumen at 188.6-535.7 ng/ml of Heal fluids (mean = 298.1 ng/ml, 17 = 11). Taken together, our results demonstrate that AKR1B10 is a new secretory protein belonging to a lysosome-mediated non-classical protein-secretion pathway and is a potential serum marker.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available