QSulf1, a heparan sulfate 6- O -endosulfatase, inhibits fibroblast growth factor signaling in mesoderm induction and angiogenesis

• DOI: 10.1073/pnas.0401028101
• Publication Date: 2004-03-30T02:03:53Z
• Authors: Shouwen Wang; Xingbin Ai; Stephen D. Freeman; Mary E. Pownall; Qun Lu; Daniel S. Kessler; Charles P. Emerson
• Keywords: Embryonic Induction; Fibroblast Growth Factors; Mesoderm; 0301 basic medicine; Xenopus laevis; 03 medical and health sciences; Reverse Transcriptase Polymerase Chain Reaction; Animals; Neovascularization, Physiologic; Sulfatases; Signal Transduction; 3. Good health

The signaling activities of multiple developmental ligands require sulfated heparan sulfate (HS) proteoglycans as coreceptors. QSulf1 and its mammalian orthologs are cell surface HS 6- O -endosulfatases that expressed in embryonic mesodermal neural progenitors promote Wnt signal transduction. In this study, we have investigated the function fibroblast growth factor (FGF) signaling, which requires 6-O-sulfated for FGF receptor (FGFR) dimerization tyrosine kinase activation. Here, report inhibits FGF2- FGF4-induced mesoderm formation Xenopus embryo FGF-dependent angiogenesis chicken through 6-O-desulfation HS. regulates inhibition HS-mediated FGFR1 activation by interfering with FGF–HS–FGFR1 ternary complex formation. Furthermore, can produce enzymatically modified soluble heparin acts a potent inhibitor FGF2-induced embryo. QSulf1, therefore, has dual regulatory functions negative regulator positive signaling. Therefore, provides another reagent to compounds, vivo vitro , modulate cellular stem cell-based therapies tissue regeneration cancer control block angiogenesis.