Expression of two different forms of fibroblast growth factor receptor 1 in different mouse tissues and cell lines.

The fibroblast growth factor receptors (FGFRs) form a multigene family of at least four members, all having extracellular regions consisting of either two or three immunoglobin-like (Ig-like) domains. By RNase protection analysis we have analyzed the expression of FGFR-1 mRNA in various tissues and cell lines and demonstrated that all of the cell lines studied expressed at least two different forms of the FGFR-1 at similar levels. Although muscle and heart express forms having either two FGFR-1 short (FGFR-1S) or three FGFR-1 long (FGFR-1L) Ig-like domains, the developing brain and adult brain express only mRNA encoding the longer form. The two forms of the receptor were characterized further by stably introducing expression vectors expressing them into Rat-2 fibroblasts and FDC-P1 myeloid cells. Treatment of the transfected Rat-2 cells with acidic FGF (aFGF) or basic FGF (bFGF) resulted in focus formation. The transformed phenotype was observed even without addition of ligand after growth in culture for greater than 2 months. Cross-linking of 125I-labeled bFGF (125I-bFGF) to Rat-2 cells expressing either FGFR-1L or FGFR-1S yielded two similar complexes of 150 and 110 kDa. Although Rat-2 cells expressing FGFR-1L yielded similar complexes with 125I-labeled aFGF (125I-aFGF), only the 150-kDa complex was formed with cells expressing FGFR-1S. The 150-kDa complex was also observed when 125I-aFGF or 125I-bFGF was cross-linked to FDC-P1 cells expressing FGFR-1L. Significantly, these complexes were only observed when heparin was present in the cross-linking reaction. FDC-P1 cells expressing FGFR-1 bound aFGF and bFGF with high affinity but only in the presence of heparin. The factor dependence of these cells could be switched from interleukin 3 to FGF in the presence of heparin.