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 osmolari ty strongly activates the c-Jun amino-terminal protein kinase (JNK) ca scade, 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 (TN F), and interleukin-1 (IL-1), Activation of the EGF and TNF receptors was also detected biochemically. Whereas activation of each receptor a lone resulted in modest activation of JNK, coadministration of EGF, IL -1, and TNF resulted in a strong synergistic response equal to that ca used by exposure to osmotic shock or UV light. Inhibition of clusterin g or receptor down-regulation attenuated both the osmotic shock and UV responses. Physical stresses may perturb the cell surface or alter re ceptor conformation, thereby subverting signaling pathways normally us ed by growth factors and cytokines.