The mammalian ultraviolet response is triggered by activation of Src tyrosine kinases.
Exposure of mammalian cells to DNA-damaging agents induces the ultraviolet (UV) response, involving transcription factor AP-1, composed of Jun and Fos proteins. We investigated the mechanism by which UV irradiation induces the c-jun gene. The earliest detectable step was activation of Src tyrosine kinases, followed by activation of Ha-Ras and Raf-1. The response to UV was blocked by tyrosine kinase inhibitors and dominant negative mutants of v-src, Ha-ras, and raf-1. This signaling cascade leads to increased phosphorylation of c-Jun on two serine residues that potentiate its activity. These results strongly suggest that the UV response is initiated at or near the plasma membrane rather than the nucleus. The response may be elicited by oxidative stress, because it is inhibited by elevation of intracellular glutathione. Using tyrosine kinase inhibitors, we demonstrate that the UV response has a protective function.
Devary
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Department of Pharmacology, University of California, San Diego, La Jolla 92093-0636.
Gottlieb
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RA
Smeal
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Karin
M
M
D002462:Cell Membrane / Q000378:metabolism; D004789:Enzyme Activation; D016758:Genes, jun / Q000528:radiation effects*; D011905:Genes, ras / Q000528:radiation effects*; D019833:Genistein; D006367:HeLa Cells; D006801:Humans; D007529:Isoflavones / Q000494:pharmacology; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D014466:Ultraviolet Rays
D007529:Isoflavones; D016755:Proto-Oncogene Proteins c-jun; D019833:Genistein; D011505:Protein-Tyrosine Kinases