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Fibroblast growth factor binding to perlecan isolated from the growth plate
Abstract 2005 MHE Conference
Leigh Westa, Prasanthi Govindraja, Xiuqin Zhangb, David M. Ornitz(b), John R. Hassell,
(a)Center for Research in Skeletal Development and Pediatric Orthopaedics,
Shriners Hospitals for Children, Tampa, FL 33612
(b)Department of Molecular Biology and Pharmacology, Washington University Medical
School,660 S. Euclid Avenue, St. Louis, MO 63310,
(c)Department of Biochemistry and Molecular Biology,College of Medicine, University of
South Florida, Tampa, FL 33612
Fibroblast growth factor (FGF)-2, FGF-9 and FGF-18 are three FGF's that have been shown to
regulate chondrocyte proliferation in the growth plate.
Heparin and heparan sulfate proteoglycans from endothelial cells have been shown to bind FGF-2.
Perlecan is present in the growth plate as a proteoglycan containing both heparan and chondroitin
sulfate chains and the phenotype of the perlecan knockout mouse shows it is necessary for the
proliferation of chondrocytes in the growth plate.
We evaluated the binding of FGF's to perlecan from the growth plate using a cationic filtration assay.
We found FGF-2 bound primary to the heparan sulfate chains on perlecan but that the core protein
was also involved in FGF-2 binding when the heparan sulfate chains were present. Removal of
Chondroitin sulfate chains on perlecan enhanced FGF-2 binding slightly. FGF-1, FGF-9 and FGF-18
showed no binding to perlecan but FGF-7 showed a low level of binding.
We also found, using recombinant FGF receptors in a separate capture assay that while the
receptors would bind to a heparin-FGF-2 complex, the receptors would not bind to the
perlecan-FGF-2 complex. Similarly, perlecan did not augment FGF-2 stimulation of [3H]-thymine
incorporation in BaF3 cells.
These data show perlecan can bind to FGF-2 by its heparan sulfate chains but that chondroitin
sulfate chains on the perlecan acts to block transfer of the bound FGF-2 to the receptor.
Abstract 2005 MHE Conference
Leigh Westa, Prasanthi Govindraja, Xiuqin Zhangb, David M. Ornitz(b), John R. Hassell,
(a)Center for Research in Skeletal Development and Pediatric Orthopaedics,
Shriners Hospitals for Children, Tampa, FL 33612
(b)Department of Molecular Biology and Pharmacology, Washington University Medical
School,660 S. Euclid Avenue, St. Louis, MO 63310,
(c)Department of Biochemistry and Molecular Biology,College of Medicine, University of
South Florida, Tampa, FL 33612
Fibroblast growth factor (FGF)-2, FGF-9 and FGF-18 are three FGF's that have been shown to
regulate chondrocyte proliferation in the growth plate.
Heparin and heparan sulfate proteoglycans from endothelial cells have been shown to bind FGF-2.
Perlecan is present in the growth plate as a proteoglycan containing both heparan and chondroitin
sulfate chains and the phenotype of the perlecan knockout mouse shows it is necessary for the
proliferation of chondrocytes in the growth plate.
We evaluated the binding of FGF's to perlecan from the growth plate using a cationic filtration assay.
We found FGF-2 bound primary to the heparan sulfate chains on perlecan but that the core protein
was also involved in FGF-2 binding when the heparan sulfate chains were present. Removal of
Chondroitin sulfate chains on perlecan enhanced FGF-2 binding slightly. FGF-1, FGF-9 and FGF-18
showed no binding to perlecan but FGF-7 showed a low level of binding.
We also found, using recombinant FGF receptors in a separate capture assay that while the
receptors would bind to a heparin-FGF-2 complex, the receptors would not bind to the
perlecan-FGF-2 complex. Similarly, perlecan did not augment FGF-2 stimulation of [3H]-thymine
incorporation in BaF3 cells.
These data show perlecan can bind to FGF-2 by its heparan sulfate chains but that chondroitin
sulfate chains on the perlecan acts to block transfer of the bound FGF-2 to the receptor.
| John Hassell, Ph.D. |
Research authored by Dr. Hassell
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List of Publications via PubMed
(NIH National Library of Medicine)
List of Publications via PubMed
(NIH National Library of Medicine)
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| Dr. Hassell's research |
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Information on The Diseases Database a cross-referenced index of human disease, and the Intute: health & life
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