Title: Membrane heparan sulfate proteoglycan-supported FGF2-FGFR1 signaling: evidence in
Authors: Zhang, Zhe
Coomans, Christien
David, Guido # ×
Issue Date: Nov-2001
Publisher: American Society for Biochemistry and Molecular Biology
Series Title: Journal of Biological Chemistry vol:276 issue:45 pages:41921-41929
Abstract: Fibroblast growth factor 2 (FGF2)-initiated FGF receptor (FGFR)-signaling
requires the assistance of heparin/heparan sulfate. Here, we evaluated the
effects of different heparan sulfate proteoglycan (HSPG)-expressing cell lines
and HSPGs derived from these cells on FGF2-induced FGFR1-phosphorylation in
heparan sulfate-negative BaF3 cells. HSPGs supplied in membrane-associated form,
by presenting cells, were all effective promotors of FGF2-initiated FGFR1
phosphorylation, independently of their nature (syndecan/glypican) or cellular
origin (human lung fibroblasts, transfected Namalwa cells, or transfected K562
cells). A treatment with heparitinase initially stimulated, but finally
completely inhibited, the activity of these presenting cells. In comparison,
equivalent amounts of soluble HSPGs, obtained by trypsinization of these cells or
by immunopurification from cell extracts, did not promote FGF2-induced
FGFR1-phosphorylation, yet removal of the less anionic species or a further
treatment with heparitinase converted these soluble fractions into potent
activators of FGF2/FGFR1 signaling. Extrapolating from current structural models,
we suggest that FGFR dimerization and autophosphorylation is supported by
cooperative "heparin-like end structures," and that cell surface association and
concentration compensate for the relative scarcity of such end structures in
native HSPGs. In this model, "proteolytic" shedding of heparan sulfate would act
as a diluting, down-regulatory mechanism, while "heparanolytic" shedding might
act as an up-regulatory mechanism, by increasing the concentration of these end
ISSN: 0021-9258
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Molecular Genetics Section (-)
Department of Human Genetics - miscellaneous
× corresponding author
# (joint) last author

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