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PMID: 1697263 Published · ppublish English Comparative Study Journal Article

Cloning and expression of two distinct high-affinity receptors cross-reacting with acidic and basic fibroblast growth factors.

The EMBO journal ·Vol. 9 ·No. 9 ·1990-09-00 ·Pages 2685-92

Dionne CA, Crumley G, Bellot F, Kaplow JM, Searfoss G, Ruta M, Burgess WH, Jaye M, Schlessinger J

Abstract

The fibroblast growth factor (FGF) family consists of at least seven closely related polypeptide mitogens which exert their activities by binding and activation of specific cell surface receptors. Unanswered questions have been whether there are multiple FGF receptors and what factors determine binding specificity and biological response. We report the complete cDNA cloning of two human genes previously designated flg and bek. These genes encode two similar but distinct cell surface receptors comprised of an extracellular domain with three immunoglobulin-like regions, a single transmembrane domain, and a cytoplasmic portion containing a tyrosine kinase domain with a typical kinase insert. The expression of these two cDNAs in transfected NIH 3T3 cells led to the biosynthesis of proteins of 150 kd and 135 kd for flg and bek, respectively. Direct binding experiments with radiolabeled acidic FGF (aFGF) or basic FGF (bFGF), inhibition of binding with native growth factors, and Scatchard analysis of the binding data indicated that bek and flg bind either aFGF or bFGF with dissociation constants of (2-15) x 10(-11) M. The high affinity binding of two distinct growth factors to each of two different receptors represents a unique double redundancy without precedence among polypeptide growth factor-receptor interactions.

MeSH Terms
Amino Acid Sequence Animals Base Sequence Cell Line Cloning, Molecular Fibroblast Growth Factors/metabolism Filaggrin Proteins Gene Expression Humans Kinetics Methionine/metabolism Mice Molecular Sequence Data Oligonucleotide Probes Polymerase Chain Reaction RNA/genetics,isolation & purification Receptors, Cell Surface/biosynthesis,genetics,metabolism Receptors, Fibroblast Growth Factor Sequence Homology, Nucleic Acid Transfection
Chemicals
FLG protein, human Filaggrin Proteins Oligonucleotide Probes Receptors, Cell Surface Receptors, Fibroblast Growth Factor Fibroblast Growth Factors RNA Methionine
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Dionne C A
Rorer Central Research, King of Prussia, PA 19406.
Crumley G
Bellot F
Kaplow J M
Searfoss G
Ruta M
Burgess W H
Jaye M
Schlessinger J
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
1990-09-00
Pages
2685-92
Language
English
Region
England
NLM ID
8208664
PMCID
PMC551973
Subset
IM
Databases
GENBANK
X52832, X52833
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