EGF receptor crosstalks with cytokine receptors leading to the activation of c-Jun kinase in response to UV irradiation in human keratinocytes

• Published in: Cellular signalling 2001-02, Vol.13 (2), p.139-144
• Main Authors: Wan, Y.S., Wang, Z.Q., Voorhees, J., Fisher, G.
• Format: Article
• Language: English
• Subjects: Adult; c-Jun; Crosstalk; EGFR; Enzyme Activation; Enzyme Inhibitors - pharmacology; Glutathione Transferase - metabolism; Humans; IL-1 receptor; Interleukin-1 - metabolism; Interleukin-1 Receptor-Associated Kinases; JNK Mitogen-Activated Protein Kinases; Keratinocyte; Keratinocytes - metabolism; Keratinocytes - radiation effects; Mitogen-Activated Protein Kinases - metabolism; Phosphorylation - radiation effects; Protein Binding - radiation effects; Protein Kinases - metabolism; Quinazolines - pharmacology; Receptor, Epidermal Growth Factor - metabolism; Signal Transduction - radiation effects; Skin; Skin - cytology; Skin - radiation effects; Time Factors; Transcription Factor AP-1 - metabolism; Ultraviolet Rays
• ISSN: 0898-6568; 1873-3913
• DOI: 10.1016/S0898-6568(00)00146-7

Ultraviolet (UV) irradiation causes photoageing through induction of matrix-degrading metalloproteinases (MMP), which are upregulated by activator protein-1 (AP-1) (Jun/Fos). The c-Jun kinase activity proves to be critically important in the regulation of AP-1 activity. Our previous studies showed that UV irradiation activates epidermal growth factor receptor (EGFR) and cytokine receptors leading to the activation of c-Jun kinase in cultured human skin keratinocytes in vitro and in human skin in vivo. However, the mechanism of UV-induced cell surface receptor activation and the crosstalk among growth factor receptor and cytokine receptors were not fully investigated. This study showed that UV (30 mJ/cm 2)-induced EGFR tyrosine phosphorylation in a manner similar to EGF (100 ng/ml), or IL-1β (10 ng/ml) in cultured human keratinocytes. In all cases, EGFR tyrosine phosphorylation was completely inhibited by pretreatment of PD153035 (100 nM, 1 h). Also observed was that UV induced autophosphorylation of interleukin 1 receptor associated kinase (IRAK) in a manner analogous to IL-1β or EGF. In both UV and EGF cases, the phosphorylation of IRAK was inhibited by pretreatment of PD153035. However, IL-1β-induced IRAK activation was not affected by PD153035. In vitro kinase assay using GST–c-Jun as a substrate revealed that pretreatment of PD153035 completely inhibited UV- and IL-1-induced c-Jun kinase activity in cultured keratinocytes. Taken together, the above data suggest that EGFR plays dominant role in the crosstalk among growth factor receptor and cytokine receptors leading to the activation of c-Jun kinase upon UV irradiation, and that EGFR could be one of the targets for clinical and cosmetical prevention of UV-induced skin aging.