Publication Date:
1993-09-10
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Devary, Y -- Rosette, C -- DiDonato, J A -- Karin, M -- CA50528/CA/NCI NIH HHS/ -- ES04151/ES/NIEHS NIH HHS/ -- New York, N.Y. -- Science. 1993 Sep 10;261(5127):1442-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology, School of Medicine, University of California at San Diego, La Jolla 92093.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8367725" target="_blank"〉PubMed〈/a〉
Keywords:
Alleles
;
Animals
;
Catechols/pharmacology
;
Cell Nucleus/*physiology
;
Cytosol/metabolism
;
Genes, ras
;
Genes, src
;
HeLa Cells
;
Humans
;
NF-kappa B/*metabolism/radiation effects
;
Nitriles/pharmacology
;
PC12 Cells
;
Phosphatidylcholines/metabolism
;
Protein-Tyrosine Kinases/metabolism
;
Proto-Oncogene Proteins/genetics
;
Proto-Oncogene Proteins c-jun/metabolism
;
Proto-Oncogene Proteins c-raf
;
Reactive Oxygen Species/metabolism
;
Signal Transduction
;
Tetradecanoylphorbol Acetate/pharmacology
;
Transfection
;
Tumor Necrosis Factor-alpha/pharmacology
;
*Tyrphostins
;
*Ultraviolet Rays
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
