tailieunhanh - Báo cáo khoa học: Early signaling events induced by 280-nm UV irradiation

The depletion of stratospheric ozone results in increasedUV (ultraviolet) light below 300 nm, and has signi®cant e ects onbiological the e ectsofUV in this range, early signaling events induced by monochro-maticUV lightwere investigatedusing the chickenBcell line DT40 andmutants lacking protein tyrosine kinases (PTKs). AmongMAPkinase familyproteins, P38MAPkinase (P38) was selectively and immediately activated by 280 nm UV light in cultured DT40 cells. | Eur. J. Biochem. 269 664-670 2002 FEBS 2002 Early signaling events induced by 280-nm UV irradiation Yukihito Kabuyama1 Miwako K. Homma1 Tomohiro Kurosaki2 and Yoshimi Homma1 1 Department of Biomolecular Science Institute of Biomedical Sciences Fukushima Medical University School of Medicine Fukushima Japan 2 Department of Molecular Genetics Institute for Hepatic Research Kansai Medical University Moriguchi Japan The depletion of stratospheric ozone results in increased UV ultraviolet light below 300 nm and has signifcant effects on biological systems. To better understand the effects of UV in this range early signaling events induced by monochromatic UV light were investigated using the chicken B cell line DT40 and mutants lacking protein tyrosine kinases PTKs . Among MAP kinase family proteins P38 MAP kinase P38 was selectively and immediately activated by 280 nm UV light in cultured DT40 cells. Activation of P38 was completely inhibited in cells deficient in Lyn and Btk. Introduction of wild-type Btk but not kinase-inactive Btk restored the P38 activation. In contrast P38 activation was not affected in Syk-deficient cells. Tyrosine phosphorylation of Lyn was induced by 280 nm UV light and pretreatment of cells with orthovanadate an inhibitor of protein tyrosine phosphatase PTP enhanced both Lyn phosphorylation and P38 activation. These results show that Lyn and Btk are upstream regulators of the P38 signaling pathway activated by 280 nm UV light and that the triggering event likely involves inactivation of PTP. Furthermore cell death induced by 280 nm UV irradiation were augmented by Btk depletion or a specifc inhibitor for P38 and partially blocked in Lyn-defcient cells suggesting that the Lyn-Btk-P38 pathway promotes cell survival while other Lyn pathways stimulate cell death. Keywords ultraviolet signal transduction protein tyrosine kinase protein tyrosine phosphatase. Ultraviolet UV sunlight is an important environmental factor in the etiology of skin cancer