The molecular biology of heparan sulfate fibroblast growth factor receptors.
Two distinct classes of cell surface FGF-binding proteins have been identified. These receptors differ in both mode of interaction and in affinity for the FGFs. cDNAs that encode the low-affinity receptor were isolated from a hamster kidney cell line cDNA library by expression cloning. Transfected cells that contained these heparan sulfate proteoglycan FGF receptor cDNAs were enriched for by panning on basic FGF-coated plates. The analogous human cDNA was isolated from a hepatoma cell line cDNA library. The homology of our hamster cDNAs to the previously described murine integral membrane proteoglycan syndecan, together with an exact amino acid sequence match of our human-cDNA-encoded product to human syndecan, clearly indicates the identity of these independently isolated proteoglycans. Further confirmation that the expressed molecule serves as a proteoglycan core protein was achieved by immunoprecipitation of 35SO4-labeled material from solubilized transfected cells. Nitrous acid treatment and chondroitinase digestion revealed that 77% of the label was associated with heparan sulfate chains and 22% with chondroitin sulfate chains. These heparan sulfate chains contributed to the fivefold increase in the total heparan sulfate found to be present on the surface of the transfected cells compared with cells transfected with a vector lacking the cDNA insert.
Kiefer
M C
MC
Chiron Corporation, Emeryville, California 94608.
Ishihara
M
M
Swiedler
S J
SJ
Crawford
K
K
Stephans
J C
JC
Barr
P J
PJ
D000595:Amino Acid Sequence; D000818:Animals; D003001:Cloning, Molecular; D006224:Cricetinae; D004247:DNA / Q000235:genetics; D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D011509:Proteoglycans / Q000235:genetics* / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000235:genetics*; D017468:Receptors, Fibroblast Growth Factor; D016415:Sequence Alignment; D053667:Syndecans
D004247:DNA; D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate; D008562:Membrane Glycoproteins; D011509:Proteoglycans; D011956:Receptors, Cell Surface; D017468:Receptors, Fibroblast Growth Factor; D053667:Syndecans