Activation of NF-κB by oncogenic Raf in HEK 293 cells occurs through autocrine recruitment of the stress kinase cascade

Abstract

Raf-1 kinase has been implicated in the induction of NF-κB activity by serum growth factors, phorbol ester and PTK oncogenes. Here we show that Raf activation of NF-κB, as measured in reporter gene assays, occurs indirectly and requires the stress kinase cascade. The stress pathway presumably becomes activated through induction of an autocrine loop by activated Raf (Raf-BXB) as suramin, the tyrphostin AG1478 and a dominant negative mutant of the EGF-R blocked NF-κB activation. Raf-BXB synergizes with SAPKs and a dominant negative mutant of SEK significantly reduces activation of NF-κB consistent with a role of this signaling pathway in the activation of NF-κB.