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J. Biol. Chem., Vol. 281, Issue 23, 15694-15700, June 9, 2006
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1
From the
Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, Missouri 63110, Department of Pharmacology, New York University School of Medicine, New York, New York 10016, ¶Department of Biological Chemistry, Molecular & Behavioral Neuroscience Institute, University of Michigan Medical School, Ann Arbor, Michigan 48109
In mammals, fibroblast growth factors (FGFs) are encoded by 22 genes. FGFs bind and activate alternatively spliced forms of four tyrosine kinase FGF receptors (FGFRs 1–4). The spatial and temporal expression patterns of FGFs and FGFRs and the ability of specific ligand-receptor pairs to actively signal are important factors regulating FGF activity in a variety of biological processes. FGF signaling activity is regulated by the binding specificity of ligands and receptors and is modulated by extrinsic cofactors such as heparan sulfate proteoglycans. In previous studies, we have engineered BaF3 cell lines to express the seven principal FGFRs and used these cell lines to determine the receptor binding specificity of FGFs 1–9 by using relative mitogenic activity as the readout. Here we have extended these semiquantitative studies to assess the receptor binding specificity of the remaining FGFs 10–23. This study completes the mitogenesis-based comparison of receptor specificity of the entire FGF family under standard conditions and should help in interpreting and predicting in vivo biological activity.
Received for publication, February 8, 2006 , and in revised form, April 3, 2006.
* This work was funded by National Institutes of Health Grants HL076664 (to D. M. O.) and DE013686 (to M. M.), a grant from the March of Dimes foundation, and a contribution from the Virginia Friedhofer Charitable Trust (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 be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
This is paper II in a series. Paper I is Ref. 12.
1 To whom correspondence should be addressed: Dept. of Molecular Biology and Pharmacology, Washington University School of Medicine, Campus Box 8103, 660 S. Euclid Ave., St. Louis, MO 63110. E-mail: dornitz{at}wustl.edu.
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