Binding of two growth factor families to separate domains of the proteoglycan betaglycan.
Cell surface proteoglycans help present some polypeptide growth factors such as basic fibroblast growth factor (bFGF) to their receptors and may act as reservoirs for others such as transforming growth factor-beta (TGF-beta). Betaglycan, a cell surface heparan sulfate/chondroitin sulfate proteoglycan that binds TGF-beta via its core protein, is shown here to bind bFGF via its heparan sulfate chains. We investigated the potential for regulation of betaglycan by its ligands in osteoblasts, a system in which bFGF and TGF-beta have complementary effects. We report here that the apparent molecular mass of betaglycan from an osteoblast-enriched primary culture of fetal rat calvaria is decreased in response to bFGF, as detected by an increased electrophoretic migration of betaglycan. The betaglycan forms expressed in bFGF-treated osteoblasts have a reduced content of heparan sulfate GAGs, without detectable changes in the content of chondroitin sulfate GAGs or the size of the core protein. bFGF did not affect the overall population of cell-surface-associated proteins identified by sulfate labeling, which contained primarily heparan sulfate, and had only small effects on the major secreted proteoglycans, which were, by contrast, chondroitin sulfate proteoglycans. The effect of bFGF on betaglycan is therefore a selective one. These results suggest that cells can interact with members of the TGF-beta and FGF families through separate domains of the same membrane proteoglycan, and can selectively regulate the bFGF-binding carbohydrate chains of this proteoglycan in response to bFGF.
Andres
J L
JL
Cell Biology and Genetics Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10021.
DeFalcis
D
D
Noda
M
M
Massagué
J
J
D016475:3T3 Cells; D000818:Animals; D001665:Binding Sites; D002478:Cells, Cultured; D005333:Fetus; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D006025:Glycosaminoglycans / Q000378:metabolism*; D006497:Heparan Sulfate / Q000302:isolation & purification / Q000378:metabolism; D008565:Membrane Proteins / Q000302:isolation & purification / Q000378:metabolism*; D051379:Mice; D008970:Molecular Weight; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism*; D011509:Proteoglycans / Q000302:isolation & purification / Q000378:metabolism*; D051381:Rats; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D016222:Fibroblast Growth Factor 2; D006025:Glycosaminoglycans; D006497:Heparan Sulfate; D008565:Membrane Proteins; D011509:Proteoglycans; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; C071736:betaglycan