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Src and Ras are involved in separate pathways in epithelial cell scattering.
- Source :
- EMBO Journal; 10/1/97, Vol. 16 Issue 19, p5904-5913, 10p
- Publication Year :
- 1997
-
Abstract
- 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<superscript>-</superscript>) and Fyn (FynK<superscript>-</superscript>) were able to exert a dominant negative effect on the scattering response. Both SH2 and SH3 domains of FynK<superscript>-</superscript> 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<superscript>-</superscript> 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<superscript>-</superscript>, 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<superscript>-</superscript> 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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 02614189
- Volume :
- 16
- Issue :
- 19
- Database :
- Complementary Index
- Journal :
- EMBO Journal
- Publication Type :
- Academic Journal
- Accession number :
- 13005781
- Full Text :
- https://doi.org/10.1093/emboj/16.19.5904