Fibroblast growth factor receptors

Details Fibroblast growth factor receptors Fibroblast growth factor receptors

C - Chemistry, Metallurgy

12

N

C12N 15/18 (2006.01) A61K 38/18 (2006.01) A61K 38/45 (2006.01) A61P 31/22 (2006.01) C07K 14/71 (2006.01) C12N 1/19 (2006.01) C12N 1/21 (2006.01) C12N 5/10 (2006.01) C12N 9/12 (2006.01) C12N 15/54 (2006.01) G01N 33/566 (2006.01) G01N 33/571 (2006.01) A61K 38/00 (2006.01)

Patent

CA 2086425

The complete cDNA cloning of two human genes previously designated flg and bek is disclosed. These genes encode for two similar but distinct 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 protein of 150 kDa and 135 kDa for flg and bek respectively. Direct binding experiments with radiolabeled acidic FGF (aFGF), basic FGF (bFGF), or kFGF inhibition of binding with native growth factors, and Scatchard analysis of the binding data indicated that bek and flg bind aFGF, bFGF, or kFGF with dissociation constants of (2-15) × 10 -11 M. The high affinity binding of three distinct growth factors to each of two different receptors represents a unique double redundancy without precedence among polypeptide growth factor/receptor interactions. The use of transformed host cells overexpressing flg or bek or biologically active fragments thereof for drug screening is disclosed.

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