Heparan and chondroitin sulfate on growth plate perlecan mediate binding and delivery of FGF-2 to FGF receptors.
Fibroblast growth factor (FGF)-2 regulates chondrocyte proliferation in the growth plate. Heparan sulfate (HS) proteoglycans bind FGF-2. Perlecan, a heparan sulfate proteoglycan (HSPG) in the developing growth plate, however, contains both HS and chondroitin sulfate (CS) chains. The binding of FGF-2 to perlecan isolated from the growth plate was evaluated using cationic filtration (CAF) and immunoprecipitation (IP) assays. FGF-2 bound to perlecan in both the CAF and IP assays primarily via the HS chains on perlecan. A maximum of 123 molecules of FGF-2 was calculated to bind per molecule of perlecan. When digested with chondroitinase ABC to remove its CS chains, perlecan augmented binding of FGF-2 to the FGFR-1 and FGFR-3 receptors and also increased FGF-2 stimulation of [(3)H]-thymidine incorporation in BaF3 cells expressing these FGF receptors. These data show that growth plate perlecan binds to FGF-2 by its HS chains but can only deliver FGF-2 to FGF receptors when its CS chains are removed.
Smith
Simone M-L
SM
Department of Molecular Medicine, College of Medicine, University of South Florida, 12901 Bruce B Downs Blvd., MDC Box 7 Tampa, FL 33612, USA.
West
Leigh A
LA
Govindraj
Prasanthi
P
Zhang
Xiuqin
X
Ornitz
David M
DM
Hassell
John R
JR
D000818:Animals; D002417:Cattle; D002809:Chondroitin Sulfates / Q000378:metabolism*; D002810:Chondroitinases and Chondroitin Lyases / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D006132:Growth Plate / Q000737:chemistry*; D019812:Heparan Sulfate Proteoglycans / Q000737:chemistry / Q000378:metabolism*; D006497:Heparan Sulfate / Q000378:metabolism*; D006801:Humans; D011133:Polysaccharide-Lyases / Q000378:metabolism; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism*
D002809:Chondroitin Sulfates; D002810:Chondroitinases and Chondroitin Lyases; D016222:Fibroblast Growth Factor 2; D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate; D011133:Polysaccharide-Lyases; D017468:Receptors, Fibroblast Growth Factor; C071927:perlecan; C021349:heparitinsulfate lyase