Regulation of secreted Frizzled-related protein-1 by heparin.
J Biol Chem
; 282(28): 20523-33, 2007 Jul 13.
Article
em En
| MEDLINE
| ID: mdl-17500071
ABSTRACT
Secreted Frizzled-related protein-1 (sFRP-1) belongs to a class of extracellular antagonists that modulate Wnt signaling pathways by preventing ligand-receptor interactions among Wnts and Frizzled membrane receptor complexes. sFRP-1 and Wnts are heparin-binding proteins, and their interaction can be stabilized by heparin in vitro. Here we report that heparin can specifically enhance recombinant sFRP-1 accumulation in a cell type-specific manner. The effect requires O-sulfation in heparin, and involves fibroblast growth factor-2 as well as fibroblast growth factor receptor-1. Interestingly, further investigation uncovers that heparin can also affect the post-translational modification of sFRP-1. We demonstrate that sFRP-1 is post-translationally modified by tyrosine sulfation at tyrosines 34 and 36, which is inhibited by the treatment of heparin. The results suggest that accumulation of sFRP-1 induced by heparin is in part due to the relative stabilization of unsulfated sFRP-1 and the direct stabilization by heparin. The study has revealed a multifaceted regulation on sFRP-1 protein by heparin.
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Base de dados:
MEDLINE
Assunto principal:
Heparina
/
Transdução de Sinais
/
Proteínas
/
Processamento de Proteína Pós-Traducional
/
Proteínas Wnt
/
Anticoagulantes
Limite:
Humans
Idioma:
En
Ano de publicação:
2007
Tipo de documento:
Article