TY - JOUR
T1 - Ultraviolet-induced phosphorylation of p70S6K at Thr389 and Thr421/Ser424 involves hydrogen peroxide and mammalian target of rapamycin but not Akt and atypical protein kinase C
AU - Huang, Chuanshu
AU - Li, Jingxia
AU - Ke, Qingdong
AU - Leonard, Stephen S.
AU - Jiang, Bing Hua
AU - Zhong, Xiao Song
AU - Costa, Max
AU - Castranova, Vincent
AU - Shi, Xianglin
PY - 2002/10/15
Y1 - 2002/10/15
N2 - The p70 S6 kinase (p70S6k) is a Ser/Thr kinase that plays an important role in cell growth, transformation, and the transition of the cell cycle in mammalian cells. Because UV radiation has been reported to induce activation of p70S6k, which is believed to play some role in the carcinogenic effects of sun exposure, the present study investigated the signaling pathways involved in this activation induced by UV radiation in mouse epidermal JB6 C141 cells. Exposure of cells to UV radiation led to marked increases in p70S6k activity and phosphorylation at Thr389 and Thr421/Ser424. UV radiation also generated reactive oxygen species as measured by electron spin resonance and by H2O2 and O2. Fluorescence staining assays in JB6 Cl 41 cells. The scavenging of UV-generated H2O2 by N-acety-L-cyteine (a general antioxidant) or catalase (a specific H2O2 scavenger) inhibited p70S6k phosphorylation at Thr389 and Thr421/Ser424, whereas pretreatment of cells with sodium formate (an ·OH radical scavenger) or superoxide dismutase (an O2, radical scavenger) did not show any inhibitory effects. Importantly, UV-induced increases in p70S6k phosphorylation at Thr389 and Thr421/Ser424 were dramatically inhibited by pretreatment of cells with rapamycin, LY294002, or PD98059, whereas overexpression of dominant-negative mutants of PKCλ/ι and Akt1 did not inhibit p70S6k phosphorylation at Thr389 and Thr421/Ser424. These results demonstrated that H2O2, phosphatidylinositol 3-kinase, and mammalian target of rapamycin were important players for UV-induced p70S6k phosphorylation at Thr389 and Thr421/Ser424, whereas Akt and atypical protein kinase C were not involved in this activation. The role of H202 in p70S6k phosphorylation at Thr389 and Thr421/Ser424 was further supported by the findings that treatment of cells with H2O2 also caused p70S6k phosphorylation at Thr389 and Thr421/Ser424.
AB - The p70 S6 kinase (p70S6k) is a Ser/Thr kinase that plays an important role in cell growth, transformation, and the transition of the cell cycle in mammalian cells. Because UV radiation has been reported to induce activation of p70S6k, which is believed to play some role in the carcinogenic effects of sun exposure, the present study investigated the signaling pathways involved in this activation induced by UV radiation in mouse epidermal JB6 C141 cells. Exposure of cells to UV radiation led to marked increases in p70S6k activity and phosphorylation at Thr389 and Thr421/Ser424. UV radiation also generated reactive oxygen species as measured by electron spin resonance and by H2O2 and O2. Fluorescence staining assays in JB6 Cl 41 cells. The scavenging of UV-generated H2O2 by N-acety-L-cyteine (a general antioxidant) or catalase (a specific H2O2 scavenger) inhibited p70S6k phosphorylation at Thr389 and Thr421/Ser424, whereas pretreatment of cells with sodium formate (an ·OH radical scavenger) or superoxide dismutase (an O2, radical scavenger) did not show any inhibitory effects. Importantly, UV-induced increases in p70S6k phosphorylation at Thr389 and Thr421/Ser424 were dramatically inhibited by pretreatment of cells with rapamycin, LY294002, or PD98059, whereas overexpression of dominant-negative mutants of PKCλ/ι and Akt1 did not inhibit p70S6k phosphorylation at Thr389 and Thr421/Ser424. These results demonstrated that H2O2, phosphatidylinositol 3-kinase, and mammalian target of rapamycin were important players for UV-induced p70S6k phosphorylation at Thr389 and Thr421/Ser424, whereas Akt and atypical protein kinase C were not involved in this activation. The role of H202 in p70S6k phosphorylation at Thr389 and Thr421/Ser424 was further supported by the findings that treatment of cells with H2O2 also caused p70S6k phosphorylation at Thr389 and Thr421/Ser424.
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M3 - Article
C2 - 12384526
AN - SCOPUS:0037108711
SN - 0008-5472
VL - 62
SP - 5689
EP - 5697
JO - Cancer Research
JF - Cancer Research
IS - 20
ER -