TY - JOUR
T1 - The role of phosphatidylinositol-3 kinase in vanadate-promoted S phase entry
AU - Zhang, Zhuo
AU - Gao, Ning
AU - He, Hengjun
AU - Huang, Chuanshu
AU - Jiang, Bing Hua
AU - Jia, Luo
AU - Shi, Xianglin
PY - 2004/1
Y1 - 2004/1
N2 - Phosphatidylinositil-3 kinase (PI3K) is a heterodimer of catalytic and regulatory subunits. It is involved in various signaling pathways and key functions of the cells. The present study investigated the role of PI3K in vanadate-induced alteration in cell cycle regulation in C141 mouse epidermal cells. Vanadate caused a time- and dose-dependent increase in PI3K activity and phosphorylation of p70 S6 kinase (p70S6K) at Thr421/Ser424 and Thr389 sites. The phosphorylation at these sites was inhibited by PI3K inhibitor, LY294002, and p70S6K mutation. Vanadate promoted S phase entry and this promotion was inhibited by LY294002 and rapmycin, a p70S6K inhibitor. Vanadate-induced enhancement in S phase entry was also inhibited in transfection with dominant negative p70S6K mutant cells. The results obtained show that vanadate is able to increase PI3K activity through phosphorylation. PI3K activated p70S6K, which phosphated protein S6, and promoted S phase entry.
AB - Phosphatidylinositil-3 kinase (PI3K) is a heterodimer of catalytic and regulatory subunits. It is involved in various signaling pathways and key functions of the cells. The present study investigated the role of PI3K in vanadate-induced alteration in cell cycle regulation in C141 mouse epidermal cells. Vanadate caused a time- and dose-dependent increase in PI3K activity and phosphorylation of p70 S6 kinase (p70S6K) at Thr421/Ser424 and Thr389 sites. The phosphorylation at these sites was inhibited by PI3K inhibitor, LY294002, and p70S6K mutation. Vanadate promoted S phase entry and this promotion was inhibited by LY294002 and rapmycin, a p70S6K inhibitor. Vanadate-induced enhancement in S phase entry was also inhibited in transfection with dominant negative p70S6K mutant cells. The results obtained show that vanadate is able to increase PI3K activity through phosphorylation. PI3K activated p70S6K, which phosphated protein S6, and promoted S phase entry.
KW - Cell cycle regulation
KW - PI3-K
KW - Signaling pathway
KW - Vanadate
KW - p70 S6 kinase
UR - http://www.scopus.com/inward/record.url?scp=0742289129&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0742289129&partnerID=8YFLogxK
U2 - 10.1023/B:MCBI.0000007279.28280.e5
DO - 10.1023/B:MCBI.0000007279.28280.e5
M3 - Review article
C2 - 14971664
AN - SCOPUS:0742289129
SN - 0300-8177
VL - 255
SP - 239
EP - 245
JO - Molecular and Cellular Biochemistry
JF - Molecular and Cellular Biochemistry
IS - 1-2
ER -