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Activation of a PKC is required for vanadate-induced phosphorylation of protein kinase B (Akt), but not p70S6k in mouse epidermal JB6 cells

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Abstract

Vanadium is a metal widely distributed in the environment. Although vanadate-containing compounds exert potent toxic effects on a wide variety of biological systems, the mechanisms by which vanadate mediates adverse effects are not well understood. The present study investigated the vanadate-induced phosphorylation of Akt and p70S6K, two kinases known to be vital for cell survival, growth, transformation, and transition of the cell cycle in mammals. Exposure of mouse epidermal JB6 cells to vanadium led to phosphorylation of Akt and p70S6K in a time- and dose-dependent manner. Vanadium exposure also caused translocation of atypical isoforms of PKC (λ, ζ) from the cytosol to the membrane, but had no effect on PKCα translocation, suggesting that the atypical PKCs (aPKC) were specifically involved in vanadium-induced cellular response. Importantly, overexpression of a dominant negative mutant PKCλ blocked Akt phosphorylation at Ser473 and Thr308, whereas it did not inhibit p70S6k phosphorylation at Thr389 and Thr421/Ser424, suggesting that aPKC activation is specifically involved in vanadium-induced activation of Akt, but not in activation of p70S6k. Furthermore, vanadium-induced p70S6k phosphorylation at Thr389 and Thr421/Ser424 and Akt phosphorylation at Thr308 occurred through a PI-3K-dependent pathway because a PI-3K dominant negative mutant inhibited induction as compared with vector control cells. These results indicate that there was a differential role of aPKC in vanadate-induced phosphorylation of Akt and p70S6k, suggesting that signal transduction pathways leading to the activation of Akt and p70S6k were different.

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Authors and Affiliations

  1. Nelson Institute of Environmental Medicine, New York University School of Medicine, 57 Old Forge Road, Tuxedo, NY, 10987, USA

    Jingxia Li, Yan Yan, Max Costa & Chuanshu Huang

  2. Department of Basic Pharmaceutical Science, West Virginia University, Morgantown, West Virginia, 26506, USA

    Sujatha Dokka

  3. Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, West Virginia, 26505, USA

    Liying Wang, Xianglin Shi & Vincent Castranova

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  1. Jingxia Li
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  2. Sujatha Dokka
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Li, J., Dokka, S., Wang, L. et al. Activation of a PKC is required for vanadate-induced phosphorylation of protein kinase B (Akt), but not p70S6k in mouse epidermal JB6 cells. Mol Cell Biochem 255, 217–225 (2004). https://doi.org/10.1023/B:MCBI.0000007277.90298.24

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  • DOI: https://doi.org/10.1023/B:MCBI.0000007277.90298.24

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