NF-kappa B activation by ultraviolet light not dependent on a nuclear signal.
Exposure of mammalian cells to radiation triggers the ultraviolet (UV) response, which includes activation of activator protein-1 (AP-1) and nuclear factor kappa B (NF-kappa B). This was postulated to occur by induction of a nuclear signaling cascade by damaged DNA. Recently, induction of AP-1 by UV was shown to be mediated by a pathway involving Src tyrosine kinases and the Ha-Ras small guanosine triphosphate-binding protein, proteins located at the plasma membrane. It is demonstrated here that the same pathway mediates induction of NF-kappa B by UV. Because inactive NF-kappa B is stored in the cytosol, analysis of its activation directly tests the involvement of a nuclear-initiated signaling cascade. Enucleated cells are fully responsive to UV both in NF-kappa B induction and in activation of another key signaling event. Therefore, the UV response does not require a signal generated in the nucleus and is likely to be initiated at or near the plasma membrane.
Devary
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Department of Pharmacology, School of Medicine, University of California at San Diego, La Jolla 92093.
Rosette
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C
DiDonato
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JA
Karin
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M
D000483:Alleles; D000818:Animals; D002396:Catechols / Q000494:pharmacology; D002467:Cell Nucleus / Q000502:physiology*; D003600:Cytosol / Q000378:metabolism; D011905:Genes, ras; D016391:Genes, src; D006367:HeLa Cells; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism* / Q000528:radiation effects; D009570:Nitriles / Q000494:pharmacology; D016716:PC12 Cells; D010713:Phosphatidylcholines / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D019908:Proto-Oncogene Proteins c-raf; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D020032:Tyrphostins; D014466:Ultraviolet Rays
D002396:Catechols; D016328:NF-kappa B; D009570:Nitriles; D010713:Phosphatidylcholines; D011518:Proto-Oncogene Proteins; D016755:Proto-Oncogene Proteins c-jun; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D020032:Tyrphostins; C060152:tyrphostin 47; D011505:Protein-Tyrosine Kinases; D019908:Proto-Oncogene Proteins c-raf; D013755:Tetradecanoylphorbol Acetate