UV-induced tyrosine phosphorylation of PKC delta and promotion of apoptosis in the HaCaT cell line.
Protein kinase C delta (PKC delta) is activated through tyrosine phosphorylation and is involved in apoptosis induction in the H(2)O(2)-treated fibroblasts. In the human keratinocyte HaCaT cell line, ultraviolet radiation, which induces apoptosis, promoted tyrosine phosphorylation and activation of PKC delta, but neither enhanced threonine phosphorylation in the activation loop nor generated the catalytic fragment of the PKC isoform. Tyrosine phosphorylation of PKC delta was prevented by a radical scavenger, N-acetyl-l-cysteine, and by a tyrosine kinase inhibitor, genistein, in the ultraviolet-irradiated keratinocyte cell line. Ultraviolet radiation-induced apoptosis was attenuated by N-acetyl-l-cysteine and genistein as well as by a PKC inhibitor, bisindolylmaleimide I. These results indicate that reactive oxygen species generated by ultraviolet radiation enhance tyrosine phosphorylation of PKC delta, and the PKC isoform thus activated by the modification reaction contributes to induction of apoptotic cell death in keratinocytes.
Fukunaga
M
M
Biosignal Research Center, Kobe University, Kobe 657-8501, Japan.
Oka
M
M
Ichihashi
M
M
Yamamoto
T
T
Matsuzaki
H
H
Kikkawa
U
U
D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D002384:Catalysis; D016923:Cell Death; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019833:Genistein / Q000494:pharmacology; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D015151:Immunoblotting; D007211:Indoles / Q000494:pharmacology; D007527:Isoenzymes / Q000378:metabolism*; D015603:Keratinocytes / Q000378:metabolism; D008301:Maleimides / Q000494:pharmacology; D008954:Models, Biological; D010766:Phosphorylation; D011233:Precipitin Tests; D020033:Protein Isoforms; D011493:Protein Kinase C / Q000378:metabolism*; D051745:Protein Kinase C-delta; D013696:Temperature; D013997:Time Factors; D014466:Ultraviolet Rays
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D007211:Indoles; D007527:Isoenzymes; D008301:Maleimides; D020033:Protein Isoforms; D006861:Hydrogen Peroxide; D019833:Genistein; C497258:PRKCD protein, human; D011493:Protein Kinase C; D051745:Protein Kinase C-delta; C070515:bisindolylmaleimide I