Cloning and expression of two distinct high-affinity receptors cross-reacting with acidic and basic fibroblast growth factors.
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.
Dionne
C A
CA
Rorer Central Research, King of Prussia, PA 19406.
Crumley
G
G
Bellot
F
F
Kaplow
J M
JM
Searfoss
G
G
Ruta
M
M
Burgess
W H
WH
Jaye
M
M
Schlessinger
J
J
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D003001:Cloning, Molecular; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D000091344:Filaggrin Proteins; D015870:Gene Expression; D006801:Humans; D007700:Kinetics; D008715:Methionine / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D016133:Polymerase Chain Reaction; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D017468:Receptors, Fibroblast Growth Factor; D012689:Sequence Homology, Nucleic Acid; D014162:Transfection
C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D015345:Oligonucleotide Probes; D011956:Receptors, Cell Surface; D017468:Receptors, Fibroblast Growth Factor; D005346:Fibroblast Growth Factors; D012313:RNA; D008715:Methionine