Troppmair J, Hartkamp J, Rapp U R
Institut für Medizinische Strahlenkunde und Zellforschung (MSZ), University of Würzburg, Germany.
Oncogene. 1998 Aug 13;17(6):685-90. doi: 10.1038/sj.onc.1201981.
Raf-1 kinase has been implicated in the induction of NF-kappa B activity by serum growth factors, phorbol ester and PTK oncogenes. Here we show that Raf activation of NF-kappa B, 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-kappa B activation. 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.
Raf-1激酶与血清生长因子、佛波酯和PTK癌基因诱导的NF-κB活性有关。我们在此表明，在报告基因检测中所测定的Raf对NF-κB的激活是间接发生的，并且需要应激激酶级联反应。应激途径可能是通过活化的Raf（Raf-BXB）诱导自分泌环而被激活的，因为苏拉明、酪氨酸激酶抑制剂AG1478和表皮生长因子受体（EGF-R）的显性负性突变体均可阻断NF-κB的激活。Raf-BXB与应激激活蛋白激酶（SAPKs）协同作用，而SEK的显性负性突变体可显著降低NF-κB的激活，这与该信号通路在NF-κB激活中的作用是一致的。
