Résumé
We have demonstrated previously that Src controls the epidermal growth factor (EGF)‐induced dispersion of NBT‐II carcinoma epithelial cells. Here we show that while only Src and Yes were expressed and activated by EGF, microinjected kinase‐inactive mutants of Src (SrcK−) and Fyn (FynK−) were able to exert a dominant‐negative effect on the scattering response. Both SH2 and SH3 domains of FynK− were required for inhibition of cell scattering. Expression of dominant‐negative N17Ras also abrogated EGF‐induced dispersion, showing that Ras is another regulator of cell dispersion. Expression of SrcK− did not alter EGF‐evoked Shc tyrosine phosphorylation, Shc–Grb2 complex formation and MAPK activation, three elements of the Ras pathway. Furthermore, the expression of Jun–Fos and Slug rescued the block induced by N17Ras but not by SrcK−, showing that Src kinases and Ras operate in separate pathways. In addition, actinomycin D inhibition of RNA synthesis repressed the ability of the activated mutant L61Ras but not that of F527Src to induce epithelial cell scattering. Since tyrosine phosphorylation of cytoskeleton‐associated proteins pp125FAK and cortactin were abolished in EGF‐stimulated SrcK− cells, we concluded that, in contrast to Ras, Src kinases may control epithelial cell dispersion in the absence of gene expression and by directly regulating the organization of the cortical cytoskeleton.