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Originally published In Press as doi:10.1074/jbc.M203034200 on May 8, 2002

J. Biol. Chem., Vol. 277, Issue 28, 25305-25312, July 12, 2002
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Functional Analysis of Cathepsin B-like Cysteine Proteases from Leishmania donovani Complex
EVIDENCE FOR THE ACTIVATION OF LATENT TRANSFORMING GROWTH FACTOR beta *

Ashwini SomannaDagger §, Vasanthakrishna MundodiDagger §, and Lashitew Gedamu

From the Department of Biological Sciences, University of Calgary, Calgary, Alberta T2N 1N4, Canada

Cathepsin B-like genes from Leishmania donovani and Leishmania chagasi have been isolated and characterized. It is a single gene, which is constitutively expressed in all the life cycle stages of the parasite. Studies using cathepsin B-specific inhibitor treatment suggested that cathepsin B does not seem to play a role in the promastigote stages of the parasite, however it aids in the parasite survival within the host macrophages. Antisense mRNA inhibition of cathepsin B gene also revealed that it plays an important role in the parasite survival within the host macrophages. Furthermore, for the first time, we have shown that Leishmania whole cell lysates as well as the recombinant cathepsin B protein cleaved human recombinant latent transforming growth factor (TGF)-beta 1 into a mature peptide releasing the latency associated protein, in a cell-free incubation system. Mink lung epithelial cell growth inhibition assay revealed that the cleaved TGF-beta 1 was biologically active, suggesting that Leishmania cathepsin B can cleave latent TGF-beta 1 into mature and active form. These results suggest that cathepsin B plays an important role in Leishmania survival within the host macrophages by activating latent TGF-beta 1.

* This work was supported in part by grants from the Canadian Institute of Health Research (CIHR) and the Natural Sciences and Engineering Council (NSERC) of Canada (to L. G.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Dagger These authors contributed equally to this work.

§ Current address: Dept. of Microbiology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr., San Antonio, TX 78229.

To whom correspondence should be addressed: Dept. of Biological Sciences, University of Calgary, 2500 University Dr. NW, Calgary, AB, Canada T2N 1N4. Fax: 403-289-9311; E-mail: lgedamu@ucalgary.ca.

Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.


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