Title: An essential oligomannosidic glycan chain in the catalytic domain of autotaxin, a secreted lysophospholipase-d
Authors: Jansen, Silvia ×
Callewaert, Nico
Dewerte, Isabelle
Andries, Maria
Ceulemans, Hugo
Bollen, Mathieu #
Issue Date: 20-Apr-2007
Series Title: Journal of Biological Chemistry vol:282 issue:15 pages:11084-91
Abstract: Autotaxin/NPP2, a secreted lysophospholipase-D, promotes cell proliferation, survival, and motility by generating the signaling molecule lysophosphatidic acid. Here we show that ectonucleotide pyrophosphatase/phosphodiesterase 2 (NPP2) is N-glycosylated on Asn-53, Asn-410, and Asn-524. Mutagenesis and deglycosylation experiments revealed that only the glycosylation of Asn-524 is essential for the expression of the catalytic and motility-stimulating activities of NPP2. The N-glycan on Asn-524 was identified as Man(8/9)GlcNAc(2), which is rarely present on mature eukaryotic glycoproteins. Additional studies show that this Asn-524-linked glycan is not accessible to alpha-1,2-mannosidase, suggesting that its non-reducing termini are buried inside the folded protein. Consistent with a structural role for the Asn-524-linked glycan, only the mutation of Asn-524 augmented the sensitivity of NPP2 to proteolysis and increased its mobility during Blue Native PAGE. Asn-524 is phylogenetically conserved and maps to the catalytic domain of NPP2, but a structural model of this domain suggests that Asn-524 is remote from the catalytic site. Our study defines an essential role for the Asn-524-linked glycan chain of NPP2.
ISSN: 0021-9258
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Pharmacology Section (-)
Biochemistry Section (Medicine) (-)
Laboratory of Biosignaling & Therapeutics
× corresponding author
# (joint) last author

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