Ultraviolet light and osmotic stress: activation of the JNK cascade through multiple growth factor and cytokine receptors.
Exposure of mammalian cells to ultraviolet (UV) light or high osmolarity strongly activates the c-Jun amino-terminal protein kinase (JNK) cascade, causing induction of many target genes. Exposure to UV light or osmotic shock induced clustering and internalization of cell surface receptors for epidermal growth factor (EGF), tumor necrosis factor (TNF), and interleukin-1 (IL-1). Activation of the EGF and TNF receptors was also detected biochemically. Whereas activation of each receptor alone resulted in modest activation of JNK, coadministration of EGF, IL-1, and TNF resulted in a strong synergistic response equal to that caused by exposure to osmotic shock or UV light. Inhibition of clustering or receptor down-regulation attenuated both the osmotic shock and UV responses. Physical stresses may perturb the cell surface or alter receptor conformation, thereby subverting signaling pathways normally used by growth factors and cytokines.
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Department of Pharmacology, Program in Biomedical Sciences, School of Medicine, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0636, USA.
Karin
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D048868:Adaptor Proteins, Signal Transducing; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D019281:Dimerization; D004789:Enzyme Activation; D004815:Epidermal Growth Factor / Q000494:pharmacology; D066246:ErbB Receptors / Q000378:metabolism*; D019084:Fluorescent Antibody Technique, Indirect; D051380:GRB2 Adaptor Protein; D006367:HeLa Cells; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D009997:Osmotic Pressure; D010766:Phosphorylation; D011506:Proteins / Q000378:metabolism; D017472:Receptors, Interleukin-1 / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D015398:Signal Transduction; D047990:TNF Receptor-Associated Factor 1; D013696:Temperature; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014466:Ultraviolet Rays
D048868:Adaptor Proteins, Signal Transducing; D051380:GRB2 Adaptor Protein; C495948:GRB2 protein, human; D007375:Interleukin-1; D011506:Proteins; D017472:Receptors, Interleukin-1; D018124:Receptors, Tumor Necrosis Factor; D047990:TNF Receptor-Associated Factor 1; D014409:Tumor Necrosis Factor-alpha; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases