FIGURE 4.

Substitution of three N-terminal residues of FGF2 for the analogous ones in FGF1 confers upon FGF2 the ability to induce proliferation of BaF3 cells ectopically expressing FGFR2b. A, comparison of the ability of FGF1, FGF2, and FGF2 mutants to induce proliferation of FGFR2b-expressing BaF3 cells. FGF10, a FGFR2b-specific ligand, was used as a positive control. Experiments were done in triplicate, and error bars reflect one S.D. The data presented are a representative example of seven independent experiments. As expected, FGF2 induced only minimal proliferation of cells expressing FGFR2b. Compared with wild type FGF2, the FGF2^F26Y, FGF2^H25N/F26Y, and FGF2^{G19F/H25N/F26Y} mutants elicit a 2.1-, 2.4-, and 2.8-fold greater response, respectively. The increase in cell proliferation induced by FGF2^F26Y, FGF2^H25N/F26Y, or FGF2^{G19F/H25N/F26Y} relative to FGF2 was statistically significant (p < 0.01). B, comparison of the ability of FGF1, FGF2, and FGF2 mutants to induce proliferation of FGFR2c-expressing BaF3 cells. The FGF2 mutants retain the ability to induce proliferation of FGFR2c-expressing cells. As expected, FGF10 fails to promote proliferation of FGFR2c-expressing cells.