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Vanadate activated Akt and promoted S phase entry.

Authors
Zhang-Z; Gao-N; He-H; Huang-C; Luo-J; Shi-X
Source
Mol Cell Biochem 2004 Jan; 255(1-2):227-237
NIOSHTIC No.
20025982
Abstract
Protein kinase B (PKB)/Akt and its upstream signal transducer, phosphatidylinosito-3 kinase (PI3K) play an essential role in control of transcription and translation, which impact cell growth, survival, and metabolism. Transcription factor E2F is a component of the downstream proliferative machinery regulated by Akt. Hyperphosphorylation of retinoblastoma protein (pRb), a pocket protein, leads to release of E2F1, resulting in transition from G1 to S phase. The present study shows that in normal C141 cells, vanadate treatment increased the percentage of cells at S phase and elevated cyclin E and cyclin A expression. Vanadate treatment triggered phosphorylation of pRb and release of E2F1. Furthermore, vanadate increased Akt kinase activity and caused its phosphorylation at Ser473 and Thr308. Inhibition of Akt by either inhibitors or transfected cells with dominant negative kinase mutant or dominant negative phosphorylation mutant decreased the percentage of the cells at the S phase induced by vanadate, and reduced both cyclin E and E2F1 expression and phosphorylation of pRb. The present study indicates that Akt plays an essential role in vanadate-induced increase in cell number at S phase and transition from G1 to S phase through E2F-pRb pathway.
Keywords
Cell-growth; Metabolism; Proteins; Cell-cultures; Cellular-reactions; Cell-function; Cell-function; Cell-metabolism; Cellular-function; Cellular-reactions; Enzyme-activity; Enzymes
Contact
X. Shi, Pathology and Physiology Research Branch, National Institute for Occupational Safety and Health, 1095 Willowdale Road, Morgantown, WV 26505
CODEN
MCBIB8
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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