A Functional Fibroblast Growth Factor-1 Immunoglobulin Fusion Protein*
- From the Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-2605
Abstract
Proteins of the fibroblast growth factor (FGF) family play diverse roles in embryonic development, angiogenesis, and wound healing. The most well studied targets of FGF activity typically are cells of mesodermal and neuroectodermal origin; in addition, expression of FGF-1 (acidic FGF) is increased at several sites of chronic immunologic injury, and recent studies show that FGF-1 also may interact with cells of the immune system. In some human T cells, FGF-1 can induce signals necessary for production of interleukin-2, a key cytokine required for T cell proliferation. To better characterize the interaction of FGF-1 with FGF receptors on T cells, a fusion protein was constructed containing a portion of the constant region of human IgG1 (Fc) at the amino terminus of FGF-1. The Fc-FGF-1 fusion protein retained FGF function as determined by stimulation of tyrosine phosphorylation and DNA synthesis in NIH 3T3 cells. Binding of the intact fusion protein to FGF receptor 1 (FGFR1) on T cells was demonstrated by immunoprecipitation of the receptor bound to Fc-FGF-1 and by flow cytometry showing binding of fusion protein to T cells expressing FGFR1. This functional Fc-FGF-1 protein should prove useful in identifying FGFR-expressing cells.
Footnotes
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↵* This work was supported by a grant-in-aid from the American Heart Association (to G. G. M.) and by National Institutes of Health Grants RO1 HL53771 (to G. G. M.) and RO1 AR43563 (to J. W. T.).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.
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↵‡ Recipient of a summer student stipend from the American College of Rheumatology.
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↵§ To whom correspondence should be addressed: A 3310 Medical Center North, Vanderbilt University Medical School, Nashville, TN 37232-2605. Tel.: 615-322-2035; Fax: 615-343-6160; E-mail:millergg{at}ctrvax.vanderbilt.edu.
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↵1 The abbreviations used are: FGF, fibroblast growth factor; FGFR, FGF receptor; IL, interleukin; BSA, bovine serum albumin; PBS, phosphate-buffered saline; FITC, fluorescein isothiocyanate; BS3, bis(sulfosuccinimidyl) suberate; KGF, keratinocyte growth factor.
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- Received January 16, 1998.
- Revision received March 24, 1998.
- The American Society for Biochemistry and Molecular Biology, Inc.
