Expression and Biological Activity of Mouse Fibroblast Growth Factor-9

doi:10.1074/jbc.271.3.1726

Expression and Biological Activity of Mouse Fibroblast Growth Factor-9 (*)

From the Department of Molecular Biology and Pharmacology, Washington University Medical School, St. Louis, Missouri 63110

^§ To whom correspondence should be addressed. Tel.: 314-362-3908; Fax: 314-362-7058; dornitz{at}pharmdec.wustl.edustl.edu.

Abstract

Receptor specificity is an essential mechanism governing the activity of fibroblast growth factors (FGF). To begin to understand the developmental role of FGF-9/glial activating factor, we have cloned and sequenced the murine FGF-9 cDNA and expressed the protein in mammalian cells and in Escherichia coli. We demonstrate that the FGF-9 protein is highly conserved between mouse and human. Receptor specificity was determined by direct binding to soluble and cell surface forms of FGF receptor (FGFR) splice variants and by the mitogenic activity on cells, which express unique FGF receptor splice variants. Our data demonstrate that FGF-9 efficiently activates the “c” splice forms of FGFR2 and FGFR3, receptors expressed in potential target cells for FGF-9. Significantly, FGF-9 also binds to and activates the “b” splice form of FGFR3, thus becoming the first FGF ligand besides FGF-1 to activate this highly specific member of the FGF receptor family.

Footnotes

↵* This work was supported in part by National Institutes of Health Grant CA60673, Training Grants 5T32HL07275 (to S. S. O.) and 5T32NS07129 (to J. S. C.), and the Beckman Young Investigator Program (to D. M. O.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore by hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The nucleotide sequence(s) reported in this paper has been submitted to the GenBank(™)/EMBL Data Bank with accession number(s) U33535.
↵¹ The abbreviations used are:

FGF

fibroblast growth factor

GAF

glial activating factor

FGFR

fibroblast growth factor receptor

PCR

polymerase chain reaction

kb

kilobase(s).
↵²D. M. Ornitz, unpublished observations.
↵³J. S. Colvin, D. G. McEwen, and D. M. Ornitz, unpublished data.
↵⁴D. M. Ornitz, unpublished data.
- Received August 14, 1995.
- Revision received November 8, 1995.