Kappa B site-dependent induction of gene expression by diverse inducers of nuclear factor kappa B requires Raf-1

The transcription factor nuclear factor kappa B (NF-kappa B) is sequestered in the cytoplasm of most cell types where it is complexed with its inhibitor (I kappa B). A large variety of agents, including growth factors, the tumor promoter phorbol 12-myristate 13-acetate, and the cytokine tumor necrosis factor alpha, initiate signal transduction pathways that converge upon the NF-kappa B-I kappa B complex, resulting in the dissociation of I kappa B and the translocation of NF-kappa B to the
more » ... s. It has been demonstrated that the phosphorylation of I kappa B is associated with NF-kappa B activation, although the kinase(s) responsible for this process in vivo remain unknown. Here we demonstrate that expression of activated forms of the GTP-binding protein Ras or of the serine/threonine kinase Raf-1 results in the activation of transcription specifically through kappa B sites. This activation appears to be dependent on NF-kappa B, since co-expression of I kappa B alpha eliminates both Ras- and Raf-1-induced transcription. In addition, through the use of a dominant negative form of Raf-1, we show that Raf-1 is a common component utilized by multiple inducers in kappa B site-driven gene expression. These results illuminate a signal transduction pathway in which NF-kappa B/Rel family members participate and also implicate a pathway responsible for kappa B site-dependent gene expression during cell growth and in immune and inflammatory responses.
doi:10.17615/xavn-cv19 fatcat:btillbmbm5amdauiyznsra3ldi