Ligand-Affinity Cloning and Structure of a Cell Surface Heparan Sulfate Proteoglycan That Binds Basic Fibroblast Growth Factor

Expression cloning of cDNAs encoding a basic fibroblast growth factor (FGF) binding protein confirms previous hypotheses that this molecule is a cell-surface heparan sulfate proteoglycan. A cDNA library constructed from a hamster kidney cell line rich in FGF receptor activity was transfected into a...

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Bibliographic Details
Published in:	Proceedings of the National Academy of Sciences - PNAS Vol. 87; no. 18; pp. 6985 - 6989
Main Authors:	Kiefer, Michael C., Stephans, James C., Crawford, Kevin, Okino, Ken, Barr, Philip J.
Format:	Journal Article
Language:	English
Published:	Washington, DC National Academy of Sciences of the United States of America 01-09-1990 National Acad Sciences
Subjects:	Amino Acid Sequence Amino acids Analytical, structural and metabolic biochemistry Animals Base Sequence Biological and medical sciences Carbohydrates Cell Line Cell lines Chondroitin Sulfate Proteoglycans - genetics Chondroitin Sulfate Proteoglycans - metabolism Cloning, Molecular Complementary DNA DNA DNA probes Fibroblast growth factor receptors Fibroblast Growth Factors - metabolism Fundamental and applied biological sciences. Psychology Gene Library genes Genetic Vectors Glycosaminoglycans - genetics hamsters Heparan Sulfate Proteoglycans Heparitin Sulfate - genetics Heparitin Sulfate - metabolism Heterosides Humans Molecular Sequence Data Oligonucleotide Probes Other biological molecules Protein Binding proteoglycans Proteoglycans - genetics Receptors Restriction Mapping Sulfates Transfection Proteoglycan Fibroblast growth factor Molecular structure Nucleotide sequence Rodentia Molecular interaction Gene library Vertebrata Mammalia Cell line Transfection Blotting assay Molecular cloning Hamster Aminoacid sequence
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Summary:	Expression cloning of cDNAs encoding a basic fibroblast growth factor (FGF) binding protein confirms previous hypotheses that this molecule is a cell-surface heparan sulfate proteoglycan. A cDNA library constructed from a hamster kidney cell line rich in FGF receptor activity was transfected into a human lymphoblastoid cell line. Clones expressing functional basic FGF binding proteins at their surfaces were enriched by panning on plastic dishes coated with human basic FGF. The amino acid sequence deduced from the isolated cDNAs revealed several interesting features, including hydrophobic signal and transmembrane domains that flank an extracellular region containing six potential attachment sites for glycosaminoglycan side chains. The structure also contains a short hydrophilic cytoplasmic tail sequence homologous to previously reported actin binding domains. Binding of basic FGF to cells expressing the binding protein could be inhibited by heparin and heparan sulfate but not by chondroitin sulfate, dermatan sulfate, or keratan sulfate. In addition to binding basic FGF, this protein or related surface proteins may function as an initial cellular attachment site for other growth factors and for viruses, such as herpes simplex virus.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0027-8424 1091-6490
DOI:	10.1073/pnas.87.18.6985