Ultraviolet Light and Osmotic Stress: Activation of the JNK Cascade Through Multiple Growth Factor and Cytokine Receptors

TLDR

UV light or high osmolarity strongly activates the JNK cascade and induces target genes, while also causing clustering and internalization of EGF, TNF, and IL‑1 receptors, indicating that physical stresses perturb cell surface receptors and subvert normal growth factor/cytokine signaling. Co‑stimulation of EGF, IL‑1, and TNF synergistically activates JNK to the same extent as UV or osmotic shock, whereas blocking receptor clustering or down‑regulation diminishes these stress responses.

Abstract

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.