The PLC-PKC cascade is required for IL-1β-dependent Erk and Akt activation: their role in proliferation

  • Authors:
    • A. R.M. Ruhul Amin
    • Yasukatu Ichigotani
    • Myat Lin Oo
    • M. Helal Uddin Biswas
    • Hong Yuan
    • Pengyu Huang
    • Naing Naing Mon
    • Michinari Hamaguchi
  • View Affiliations

  • Published online on: December 1, 2003     https://doi.org/10.3892/ijo.23.6.1727
  • Pages: 1727-1731
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Abstract

We investigated the signaling mechanisms that lead to IL-1β-induced cell proliferation. Treatment of Balb 3T3 cells with IL-1β activated two signaling pathways, Erk and Akt. IL-1β also increased tyrosine phosphorylation of PLC-γ in Src kinase-dependent manner. Pharmacological inhibition of the PLC-PKC cascade by using specific inhibitor for PLC-γ (U73122) and PKC (GFX) strongly inhibited IL-1β-induced Erk and Akt activation. Inhibition of MEK1 by its specific inhibitor, PD98059 substantially inhibited Erk activation. Similarly, inhibition of PI3K activation by its specific inhibitor LY294002 suppressed Akt phosphorylation. Moreover, IL-1β-induced association of PLC-γ with SHPS-1. SHPS-1 mutants lacking the tyrosine phosphorylation sites failed to associate with PLC-γ. Finally, IL-1β-induced proliferation of Balb 3T3 cells and inhibition of Erk and Akt signalings or their upstream signaling molecules, Src kinase and PKC by their inhibitors strongly inhibited IL-1β-dependent cell proliferation. Taken together, our results suggest that a SHPS-1-PLC-γ complex activate the PLC-PKC cascade, which is required for the activation of IL-1β-dependent Erk and Akt signalings and cell proliferation.

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December 2003
Volume 23 Issue 6

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Amin AR, Ichigotani Y, Oo ML, Biswas MH, Yuan H, Huang P, Mon NN and Hamaguchi M: The PLC-PKC cascade is required for IL-1β-dependent Erk and Akt activation: their role in proliferation. Int J Oncol 23: 1727-1731, 2003
APA
Amin, A.R., Ichigotani, Y., Oo, M.L., Biswas, M.H., Yuan, H., Huang, P. ... Hamaguchi, M. (2003). The PLC-PKC cascade is required for IL-1β-dependent Erk and Akt activation: their role in proliferation. International Journal of Oncology, 23, 1727-1731. https://doi.org/10.3892/ijo.23.6.1727
MLA
Amin, A. R., Ichigotani, Y., Oo, M. L., Biswas, M. H., Yuan, H., Huang, P., Mon, N. N., Hamaguchi, M."The PLC-PKC cascade is required for IL-1β-dependent Erk and Akt activation: their role in proliferation". International Journal of Oncology 23.6 (2003): 1727-1731.
Chicago
Amin, A. R., Ichigotani, Y., Oo, M. L., Biswas, M. H., Yuan, H., Huang, P., Mon, N. N., Hamaguchi, M."The PLC-PKC cascade is required for IL-1β-dependent Erk and Akt activation: their role in proliferation". International Journal of Oncology 23, no. 6 (2003): 1727-1731. https://doi.org/10.3892/ijo.23.6.1727