Journal
FEBS LETTERS
Volume 579, Issue 11, Pages 2334-2338Publisher
WILEY
DOI: 10.1016/j.febslet.2005.03.030
Keywords
heparanase; protease; lysosome; endosome; fractionation; processing
Funding
- NCI NIH HHS [R01 CA106456-01] Funding Source: Medline
Ask authors/readers for more resources
Heparanase is an endo-beta-glucuronodase involved in cleavage of heparan sulfate side chains, activity that is strongly implicated in cell dissemination associated with tumor metastasis and inflammation. Heparanase is first synthesized as a latent 65 kDa precursor that is converted into an active enzyme upon proteolytic processing. Previously, we have reported that elevation of the lysosomal pH results in complete inhibition of heparanase processing, suggesting that lysosomal protease(s) and acidic pH conditions are required for heparanase processing. Here, we adopted a cell fractionation approach and provide evidence that incubation of the pro-enzyme with lysosome/endosome, but not with cytoplasmic fractions resulted in processing and activation of the 65 kDa latent heparanase. Moreover, while the water soluble lysosome/endosome fraction exhibited no apparent processing activity, heparanase processing by the water insoluble lysosome/endosome membrane fraction was readily detected and exhibited the expected pH dependency. (c) 2005 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
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