Activation of NF-kappa B by oncogenic Raf in HEK 293 cells occurs through autocrine recruitment of the stress kinase cascade.
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.
Troppmair
J
J
Institut für Medizinische Strahlenkunde und Zellforschung (MSZ), University of Würzburg, Germany.
Hartkamp
J
J
Rapp
U R
UR
D016475:3T3 Cells; D000818:Animals; D019898:Autocrine Communication; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D004789:Enzyme Activation; D066246:ErbB Receptors / Q000235:genetics; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D048728:MAP Kinase Kinase Kinase 1; D051379:Mice; D020928:Mitogen-Activated Protein Kinases; D009154:Mutation; D016328:NF-kappa B / Q000096:biosynthesis*; D009570:Nitriles / Q000494:pharmacology; D011494:Protein Kinases / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D019908:Proto-Oncogene Proteins c-raf / Q000378:metabolism*; D011799:Quinazolines / Q000494:pharmacology; D013498:Suramin / Q000494:pharmacology; D020032:Tyrphostins; D018631:ras Proteins / Q000378:metabolism
D016328:NF-kappa B; D009570:Nitriles; D011799:Quinazolines; D020032:Tyrphostins; C101044:RTKI cpd; D013498:Suramin; D011494:Protein Kinases; D066246:ErbB Receptors; D017346:Protein Serine-Threonine Kinases; D019908:Proto-Oncogene Proteins c-raf; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048728:MAP Kinase Kinase Kinase 1; C482576:MAP3K1 protein, human; C482578:Map3k1 protein, mouse; D018631:ras Proteins