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Molecular and Cellular Biochemistry

, Volume 255, Issue 1–2, pp 239–245 | Cite as

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

  • Zhuo Zhang
  • Ning Gao
  • Hengyun He
  • Chuanshu Huang
  • Bing-hua Jiang
  • Luo Jia
  • Xianglin Shi
Article

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.

vanadate PI3-K p70 S6 kinase signaling pathway cell cycle regulation 

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Copyright information

© Kluwer Academic Publishers 2004

Authors and Affiliations

  • Zhuo Zhang
    • 1
    • 2
  • Ning Gao
    • 3
  • Hengyun He
    • 3
  • Chuanshu Huang
    • 4
  • Bing-hua Jiang
    • 3
  • Luo Jia
    • 3
  • Xianglin Shi
    • 1
  1. 1.Pathology and Physiology Research BranchNational Institute for Occupational Safety and HealthMorgantown
  2. 2.Department of Basic Pharmaceutical SciencesWest Virginia UniversityMorgantown
  3. 3.Mary Babb Randolph Cancer Center, Department of Microbiology, Immunology and Cell BiologyWest Virginia UniversityMorgantownUSA
  4. 4.Nelson Institute of Environmental Medicine, New York University School of MedicineNew YorkUSA

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