Inhibition or activation of apert syndrome FGFR2 (S252W) signaling by specific glycosaminoglycans

Lynda M. McDowell, Beth A. Frazier, Daniel R. Studelska, Kari Giljum, Jinghua Chen, Jian Liu, Kai Yu, David M. Ornitz, Lijuan Zhang

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

Abstract

Most Apert syndrome patients harbor a single amino acid mutation (S252W) in fibroblast growth factor (FGF) receptor 2 (FGFR2), which leads to abnormal FGF/FGFR2 signaling. Here we show that specific combinations of FGFs and glycosaminoglycans activate both alternative splice forms of the mutant but not of the wild-type FGF receptors. More importantly, 2-O- andN-sulfated heparan sulfate, prepared by a combined chemical and enzymatic synthesis, antagonized the over-activated FGFR2b (S252W) to basal levels at nanomolar concentrations. These studies demonstrated that specific glycosaminoglycans could be useful in treating ligand-dependent FGFR signaling-related diseases, such as Apert syndrome and cancer.

Original languageEnglish
Pages (from-to)6924-6930
Number of pages7
JournalJournal of Biological Chemistry
Volume281
Issue number11
DOIs
StatePublished - Mar 17 2006

Fingerprint

Dive into the research topics of 'Inhibition or activation of apert syndrome FGFR2 (S252W) signaling by specific glycosaminoglycans'. Together they form a unique fingerprint.

Cite this