Title: Domain Interplay Mediated by an Essential Disulfide Linkage Is Critical for the Activity and Secretion of the Metastasis-promoting Enzyme Autotaxin
Authors: Jansen, Silvia
Andries, Maria
Derua, Rita
Waelkens, Etienne
Bollen, Mathieu # ×
Issue Date: May-2009
Publisher: Amer soc biochemistry molecular biology inc
Series Title: Journal of Biological Chemistry vol:284 issue:21 pages:14296-14302
Abstract: Autotaxin or NPP2 (nucleotide pyrophosphatase/phosphodiesterase 2) is a secreted lysophospholipase-D that promotes metastasis and tumor growth by its ability to generate lysophosphatidic acid. Considerable evidence suggests that inhibitors of NPP2 can be used as a novel therapy for the treatment of cancer. Although most attention is currently directed toward the development of inhibitors of the catalytic site, we have explored whether NPP2 can also be targeted through its non-catalytic nuclease-like domain. We demonstrate here that the catalytic and nuclease-like domains are covalently linked by an essential disulfide bridge between Cys(413) and Cys(805). Within the nuclease-like domain, residues 829-850 are involved in the secretion of NPP2, and Lys(852) is required for the expression of catalytic activity. These data show that the nuclease-like domain is crucial for catalysis by NPP2 and is a possible target to generate inhibitors.
ISSN: 0021-9258
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Biosignaling & Therapeutics
Laboratory of Protein Phosphorylation and Proteomics
Laboratory of Phosphoproteomics (-)
× corresponding author
# (joint) last author

Files in This Item:

There are no files associated with this item.

Request a copy


All items in Lirias are protected by copyright, with all rights reserved.

© Web of science