Fy. Zhou et al., IS THE SENSITIVITY OF CELLS FOR FGF-1 AND FGF-2 REGULATED BY CELL-SURFACE HEPARAN-SULFATE PROTEOGLYCANS, European journal of cell biology, 73(2), 1997, pp. 166-174
We have examined the importance of cell surface heparan sulfate proteo
glycans (HSPG) in fibroblast growth factor (FGF) signaling, 3T3 cells
grown under conventional conditions were much more sensitive to FGF-2
compared to FGF-1. However, cells were equally sensitive to FGF-1 and
FGF-2 using conditions which reduced the effect of endogenous HSPG. Ad
dition of heparin, or treatment with chlorate, an inhibitor of proteog
lycan sulfation, resulted in enhanced or reduced growth factor respons
e, respectively, and eliminated the differences between FGF-1 and FGF-
2. HSPGs isolated from trypsin digests of 3T3 cells had a much higher
affinity for FGF-2 compared to that for FGF-1 when analyzed by affinit
y chromatography Glycosaminoglycan chains or core protein fragments de
rived from the HSPG failed to show the same high apparent affinity for
FGF-2, suggesting that an intact proteoglycan structure was important
for tile high FGF-2 affinity. Addition of HSPG ectodomains, isolated
from cultured 3T3 cells or produced as recombinant molecules, to chlor
ate-treated cultures of 3T3 cells inhibited the mitogenic activity of
FGF-2 and eliminated the effect of heparin as a potentiator of either
growth factor These results support the idea that tile cell-associated
HSPG is an integral component of the FGF signaling system and in 3T3
cells contributes to the increased sensitivity of these cells to FGF-2
compared to FGF-1. Since isolated ectodomains of HSPG inhibited rathe
r than simulated tile mitogenic response of the FGFs, the proper ancho
ring of the HSPG in tile cell membrane appears to be important for a s
timulatory effect.