Exogenous FGF-2 added to cells is internalized and part of it translocates to the nucleus of the cells. To get a better understanding of the FGF-2-induced signaling pathway, we looked for proteins associated with FGF-2 in the cytoplasm of the target cells. We first used the GST-FGF-2 to isolate cytoplasmic proteins complexes containing FGF-2 from S100 extract (supernatant 100,000g). Among the retrieved proteins, we focused our studies on RPS19, a protein of the 40S small ribosomal subunit. We showed that FGF-2 interacts directly with RPS19 in vitro. Second, we coimmunoprecipitated RPS19 and FGF-2 from a S240 extract (240,000g supernatant) prepared from FGF-2-stimulated cells and devoid of 40S ribosomal subunit. The result of these experiments suggest that a pool of free RPS19 exists in cells and that FGF-2 interacts in vivo with free RPS19.