A functional fibroblast growth factor-1 immunoglobulin fusion protein.
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.
Dikov
M M
MM
Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-2605, USA.
Reich
M B
MB
Dworkin
L
L
Thomas
J W
JW
Miller
G G
GG
D016475:3T3 Cells; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000378:metabolism; D004261:DNA Replication; D004167:Diphtheria Toxin / Q000235:genetics / Q000378:metabolism; D016220:Fibroblast Growth Factor 1 / Q000235:genetics / Q000378:metabolism*; D005434:Flow Cytometry; D006493:Heparin / Q000378:metabolism; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000235:genetics / Q000378:metabolism*; D019169:Jurkat Cells; D051379:Mice; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013205:Staphylococcal Protein A / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism
D000888:Antibodies, Anti-Idiotypic; D004167:Diphtheria Toxin; D007141:Immunoglobulin Fc Fragments; D010446:Peptide Fragments; D017468:Receptors, Fibroblast Growth Factor; D011993:Recombinant Fusion Proteins; D013205:Staphylococcal Protein A; C048844:anti-IgG; C029795:diphtheria toxin fragment A; D016220:Fibroblast Growth Factor 1; D014443:Tyrosine; D006493:Heparin; C496348:FGFR1 protein, human; C496349:Fgfr1 protein, mouse; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1