Receptor Specificity of the Fibroblast Growth Factor Family

doi:10.1074/jbc.271.25.15292

Receptor Specificity of the Fibroblast Growth Factor Family*

From the ^‡ Department of Molecular Biology and Pharmacology,
^¶ Department of Pediatrics, Washington University Medical School, St. Louis, Missouri 63110, the
^∥ INSERM Unite 119, 27 bd Lei Roure, 13009 Marseille, France, the
^”Department of Biochemistry and Molecular Biophysics, Columbia University College of Physicians and Surgeons, New York, New York 10032, and the
^‴ Brookdale Center for Molecular Biology, Mount Sinai School of Medicine, New York, New York 10029

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

Abstract

Fibroblast growth factors (FGFs) are essential molecules for mammalian development. The nine known FGF ligands and the four signaling FGF receptors (and their alternatively spliced variants) are expressed in specific spatial and temporal patterns. The activity of this signaling pathway is regulated by ligand binding specificity, heparan sulfate proteoglycans, and the differential signaling capacity of individual FGF receptors. To determine potentially relevant ligand-receptor pairs we have engineered mitogenically responsive cell lines expressing the major splice variants of all the known FGF receptors. We have assayed the mitogenic activity of the nine known FGF ligands on these cell lines. These studies demonstrate that FGF 1 is the only FGF that can activate all FGF receptor splice variants. Using FGF 1 as an internal standard we have determined the relative activity of all the other members of the FGF family. These data should serve as a biochemical foundation for determining developmental, physiological, and pathophysiological processes that involve FGF signaling pathways.

Footnotes

↵* This work was supported by Grant CA60673 from the National Institutes of Health and by 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. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
↵¹ The abbreviations used are:

FGF

fibroblast growth factor

FGFR

fibroblast growth factor receptor.
↵² D. M. Ornitz, M. Goldfarb, and A. Chellaiah, unpublished data.
↵³ D. M. Ornitz, J. Xu, G. Cao, and M. Goldfarb, unpublished data.
↵⁴ A. Chellaiah and D. M. Ornitz, unpublished data.
↵⁵ G. Gao and M. Goldfarb, unpublished data.
- Received January 31, 1996.
- Revision received March 15, 1996.