A FUNCTIONAL FIBROBLAST GROWTH-FACTOR-I IMMUNOGLOBULIN FUSION PROTEIN

Proteins of the fibroblast growth factor (FGF) family play diverse rol es in embryonic development, angiogenesis, and wound healing. The most well studied targets of FGF activity typically are cells of mesoderma l 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 im mune system. In some human T cells, FGF-1 can induce signals necessary for production of interleukin-a, a key cytokine required for T cell p roliferation. To better characterize the interaction of FGF-1 with FGF receptors on T cells, a fusion protein was constructed containing a p ortion 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 determ ined by stimulation of tyrosine phosphorylation and DNA synthesis in N IH 3T3 cells. Binding of the intact fusion protein to FGF receptor 1 ( FGFR1) on T cells was demonstrated by immunoprecipitation of the recep tor 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.