IS THE SENSITIVITY OF CELLS FOR FGF-1 AND FGF-2 REGULATED BY CELL-SURFACE HEPARAN-SULFATE PROTEOGLYCANS

Citation
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
Citations number
47
Categorie Soggetti
Cell Biology
ISSN journal
01719335
Volume
73
Issue
2
Year of publication
1997
Pages
166 - 174
Database
ISI
SICI code
0171-9335(1997)73:2<166:ITSOCF>2.0.ZU;2-7
Abstract
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.