FGF-2 DIMERIZATION INVOLVEMENT IN GROWTH-FACTOR MEDIATED CELL-PROLIFERATION BUT NOT CELL-DIFFERENTIATION

Dimerization is a prerequisite for many growth factors in their recept or activation leading to cellular response. FGF-1 and FGF-2, members o f the Fibroblast Growth Factor (FGF) family, were shown to form noncov alent dimers and oligomers in vitro. Using the two-hybrid system as an in vivo binding assay we show here that of three representative membe rs of the FGF family, only FGF-2 is able to homodimerize. Moreover the FGF-S isoforms could heterodimerize. Two single-point mutants (T121F and W123R), defective in their dimerization capability, were isolated through random mutagenesis and were used to study the role of FGF-S di merization with regard to its biological activity. Remarkably, these m utant proteins were still able to induce cell differentiation, but wer e strongly affected in their capacity to promote cell proliferation. T his study thus highlights the uncoupling between proliferation and dif ferentiation FGF-S signaling pathways and the crucial role of FGF-2 di merization in the mitogenic activity of this factor. (C) 1998 Academic Press.