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The role of phosphatidylinositol-3 kinase in vanadate-promoted S phase entry.

Authors
Zhang-Z; Geo-N; He-H; Huang-C; Jiang-B; Jia-L; Shi-X
Source
Mol Cell Biochem 2004 Jan; 255(1-2):239-245
NIOSHTIC No.
20024353
Abstract
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.
Keywords
Epidemiology; Inhalation-studies; Particulates; Airborne-particles; Cardiopulmonary-system-disorders; Lung-cancer; Exposure-levels; Metal-dusts; Metallic-dusts; Metallic-ions; Author Keywords: vanadate; PI3-K; p70 S6 kinase; signaling pathway; cell cycle regulation
Contact
Pathology and Physiology Research Branch, National Institute for Occupational Safety and Health, Morgantown, WV 26505, USA
CODEN
MCBIB8
CAS No.
13721-39-6
Publication Date
20040101
Document Type
Journal Article
Email Address
xshi@cdc.gov
Fiscal Year
2004
NTIS Accession No.
NTIS Price
Issue of Publication
1-2
ISSN
0300-8177
NIOSH Division
HELD
Source Name
Molecular and Cellular Biochemistry
State
WV; NY
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