ACTIVATION OF NF-KAPPA-B BY ONCOGENIC RAF IN HEK-293 CELLS OCCURS THROUGH AUTOCRINE RECRUITMENT OF THE STRESS KINASE CASCADE

Raf-l kinase has been implicated in the induction of NF-kappa B activi ty by serum growth factors, phorbol ester and PTK oncogenes. Here we s how that Raf activation of NF-kappa B, as measured in reporter gene as says, occurs indirectly and requires the stress kinase cascade. The st ress pathway presumably becomes activated through induction of an auto crine loop by activated Raf (Raf-BXB) as suramin, the tyrphostin AG147 8 and a dominant negative mutant of the EGF-R blocked NF-kappa B activ ation. Raf-BXB synergizes with SAPKs and a dominant negative mutant of SEK significantly reduces activation of NF-kappa B consistent with a role of this signaling pathway in the activation of NF-kappa B.