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Role of Rac GTPase in the nuclear signaling by EGF
Author(s) -
Kim Byung-Chul,
Kim Jae-Hong
Publication year - 1997
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(97)00289-5
Subject(s) - epidermal growth factor , signal transduction , microbiology and biotechnology , gtpase , serum response element , mediator , chemistry , small gtpase , phospholipase c , rac gtp binding proteins , serum response factor , biology , gene , rac1 , gene expression , receptor , biochemistry
The role of Rac in epidermal growth factor (EGF)‐induced c‐fos serum response element (SRE) activation was examined in Rat‐2 fibroblast cells. By reporter gene analysis following transient or stable transfections with pEXV‐RacN17 encoding a dominant‐negative mutant of Rac, EGF‐induced activation of c‐fos SRE‐luciferase gene was shown to be selectively inhibited, suggesting that Rac activity is necessary for the full activation of SRE by EGF. Our further study to analyze the downstream mediator of Rac in EGF‐signaling cascade demonstrated that there is a functional link between Rac and phospholipase A 2 (PLA 2 ) activation and further that PLA 2 mediates, at least partly, the Rac signaling to SRE. Together, our results point to a critical role of Rac and Rac‐activated PLA 2 in the EGF‐signaling cascade to c‐fos SRE. We propose that `Rac‐PLA 2 ' cascade is one of the major signaling pathways by which EGF stimulates c‐fos SRE.