Differential Stimulation of ERK and JNK Activities by Ultraviolet B Irradiation and Epidermal Growth Factor in Human Keratinocytes

Abstract

Exposure of mammalian cells to solar ultraviolet (UV) radiation leads to the expression of several genes, and UV has been recognized as a major initiator and promoter of skin cancer. The component of the solar radiation that contributes most to human skin malignancy is UVB (280-320 nm) and, to a lesser extent, UVA (320-400 nm), whereas the high-energy UVC (100-280 nm) is absorbed by the earth's upper atmosphere. Sublethal doses of UVB produce strong induction of c-jun and c-fos transcripts in several cells including human primary keratinocytes. The present report confirms that this is also the case in the HaCaT cell line and shows that similar UVB doses are potent inducers of the JNK/SAPK family of mitogen-activated protein kinases but only weak activators of ERKs. Epidermal growth factor (EGF) caused rapid induction of both JNK- and ERK-signaling pathways, and the downmodulation of the EGF-signaling pathway by EGF pre-treatment inhibited the UVB-induced JNK1 activation. Prior UVB irradiation of the cells decreased the level of the ERK2 activation by a subsequent EGF treatment, but this sensitized the cells and allowed for the super-activation of JNK1 after a rechallenge with either UVB or EGF. The antioxidant N-acetylcysteine impaired the UVB- and EGF-induced activation of JNK1. Our data suggest the presence of shared signaling component(s) in the UVB- and EGF-induced cellular response pathways and imply that oxidative stress plays a significant role in the activation of JNK1 by UVB and EGF.

Differential phosphorylation of mitogen-activated protein kinase families by epidermal growth factor and ultraviolet B irradiation in SV40-transformed human keratinocytes

“…In the present study, we Stimulation of EGF receptor is known to induce cell proliferation [2,20]. This is associated with ERK activation at 5-60 min following the stimulation of EGF receptor [21,22], that is occasionally accompanied by JNK activation [23][24][25]. In SVHK cells, EGF activated ERK and JNK, that were associated with cell proliferation.…”

“…The In many cells including keratinocytes, UVB irradiation-induced apoptosis depends on p38 [9,17,31]. Still UVB-induced activation of ERK and JNK has been reported in normal human keratinocytes and in HaCaT cells [24]. In COS1 cells, UVC activates JNK that binds to transactivation domain of c-Jun, playing an important role on tumor promotion [7].…”

Comparative studies of a new subfamily of human Ste20-like kinases: homodimerization, subcellular localization, and selective activation of MKK3 and p38

“…Using both transiently transfected COS-1 cells, as well as by examining endogenous hKFC kinases in DU-145 and Jurkat cells using antipeptide antibodies that recognize each isoform specifically, we applied cytokines such as TNF-a and IL-1, stressors such as osmolar shock, UV irradiation and anisomycin, as well as DNA-damaging reagents (i.e., cis-platinum), all of which caused no changes in endogenous or overexpressed hKFCs kinase activities (autophosphorylation or substrate phosphorlylation) (data not shown). We also tested several growth factors, which have been shown to activate either JNK/SAPK (Bost et al, 1999) or p38 (Assefa et al, 1997) (Rousseau et al, 1997;Xing et al, 1998) in certain situations, such as epidermal growth factor (EGF), platelet-derived growth factor (PDGF), and insulin, with no detectable changes in kinase activities observed. The elusive nature of Figure 3 Comparison of hKFC kinase activities.…”

“…The first identified was extracellular-regulated kinases (ERKs), which are activated by growth-promoting reagents such as hormones and growth factors (Boulton et al, 1991;Charest et al, 1993;Peraldi et al, 1993;Assefa et al, 1997). The other two MAPK members, SAPK/JNK and p38/mHOG, are involved in stress-induced signaling mechanisms.…”

Image-guided genomic analysis of tissue response to laser-induced thermal stress

“…Cutaneous defensive mechanisms are highly complex and involve DNA repair, release of proinflammatory intercellular signaling molecules, and activation of specific signal transduction cascades that result in activation of transcription factors and regulation of gene expression. [7][8][9][10][11][12][13] The increased usage of lasers in medicine, research, and military applications has caused an increase in laser injury, particularly to the eye. 14 Laser damage to tissue can be categorized into three basic types: photomechanical, photochemical, and photothermal.…”