Aldo-keto reductase family 1, member B10 is secreted through a lysosome-mediated non-classical pathway.
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Luo DX, Huang MC, Ma J, Gao Z, Liao DF, Cao D
Aldo-keto reductase family 1, member B10 is secreted through a lysosome-mediated non-classical pathway.
Biochem J. 2011 Aug 15;438(1):71-80. doi: 10.1042/BJ20110111.
- PubMed ID
- 21585341 [ View in PubMed]
- Abstract
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 GTPgammaS 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 ileal fluids (mean=298.1 ng/ml, n=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.