| Fibroblast growth factor-binding proteins (FGF-BPs) are a family of secreted proteins that bind specific fibroblast growth factors (FGFs) and function as chaperone molecules to deliver these growth factors to their target cell surface receptors. FGF-BP1 has been shown to play a positive role in regulating FGF-dependent signaling and has been implicated as a gene responsible for an angiogenic switch in malignant progression. A second family member, FGF-BP2 is located on the same chromosome as FGF-BP1 and may share similar activity. For the present studies, a new family member, FGF-BP3, has been identified and isolated in the human and mouse genome, observed for tissue specific expression profiles, and characterized for the potential ability to modulate FGF-dependent activity. We report high levels of FGF-BP3 mRNA expression in human specimens of neuroblastoma. Examination of mouse embryos reveals a specific temporal pattern of FGF-BP3 mRNA expression, with peaks occurring at d.p.c 10.5 through d.p.c 16.5. In contrast, FGF-BP3 mRNA is below detection levels in many organs of adult mice, with the notable exception of the brain and eye. Coincident with FGF-BP1, FGF-BP3 can directly bind FGF-2 in a cell-free system. FGF-BP3 enhances FGF-2-dependent MAPK activation and cellular proliferation in NIH-3T3 fibroblasts and SW-13 adrenal carcinoma cells and promotes anchorage independent growth of SW-13 cells. Overall, our studies indicate that FGF-BP3 acts in a similar yet tissue specific manner as FGF-BP1 to support FGF-dependent biological activities. |
