Publication Date:
1996-11-15
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rosette, C -- Karin, M -- New York, N.Y. -- Science. 1996 Nov 15;274(5290):1194-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉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.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8895468" target="_blank"〉PubMed〈/a〉
Keywords:
*Adaptor Proteins, Signal Transducing
;
Calcium-Calmodulin-Dependent Protein Kinases/*metabolism
;
Dimerization
;
Enzyme Activation
;
Epidermal Growth Factor/pharmacology
;
Fluorescent Antibody Technique, Indirect
;
GRB2 Adaptor Protein
;
HeLa Cells
;
Humans
;
Interleukin-1/pharmacology
;
JNK Mitogen-Activated Protein Kinases
;
*Mitogen-Activated Protein Kinases
;
*Osmotic Pressure
;
Phosphorylation
;
Proteins/metabolism
;
Receptor, Epidermal Growth Factor/*metabolism
;
Receptors, Interleukin-1/*metabolism
;
Receptors, Tumor Necrosis Factor/*metabolism
;
Signal Transduction
;
TNF Receptor-Associated Factor 1
;
Temperature
;
Tumor Necrosis Factor-alpha/pharmacology
;
*Ultraviolet Rays
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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