Insulin activates caspase-3 by a phosphatidylinositol 3'-kinase-dependent pathway

Jonathan P. Godbout, Keith A. Cengel, Shu Ling Cheng, Christian T Minshall, Keith W. Kelley, Gregory G. Freund

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Activation of the caspase proteases by c-Jun N-terminal kinase 1 (JNK1) has been proposed as a mechanism of apoptotic cell death. Here we report that insulin activates caspase-3 by a pathway requiring phosphatidylinositol 3'-kinase (PI3-kinase). JNK1 assays demonstrated that insulin treatment of myeloma cells induced 3-fold activation of JNK1. Inhibition of PI3-kinase with wortmannin and LY294002 blocked insulin-dependent activation of JNK1. Caspase assays demonstrated that insulin increased caspase-3 activity 3-fold and that inhibition of PI3-kinase blocked this effect. Cell death was doubled by insulin and was due to a 3-fold increase in apoptosis of cells in the G1/G0 phase of the cell cycle. Inhibition of PI3-kinase completely blocked this effect. Finally, inhibition of caspase-3 with benzyloxycarbonyl-Asp-2,6-dichlorobenzoyloxymethylketone blocked cell death due to insulin. Taken together, these findings indicate that insulin activates caspase-3 by a PI3-kinase-dependent pathway resulting in increased apoptosis and cell death. Copyright (C) 1998 Elsevier Science Inc.

Original languageEnglish (US)
Pages (from-to)15-23
Number of pages9
JournalCellular Signalling
Volume11
Issue number1
DOIs
Publication statusPublished - Jan 1999

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Keywords

  • Apoptosis
  • c-Jun N-terminal kinase
  • Caspase-3
  • Insulin
  • Phosphatidylinositol 3'-kinase
  • Signal transduction

ASJC Scopus subject areas

  • Cell Biology

Cite this

Godbout, J. P., Cengel, K. A., Cheng, S. L., Minshall, C. T., Kelley, K. W., & Freund, G. G. (1999). Insulin activates caspase-3 by a phosphatidylinositol 3'-kinase-dependent pathway. Cellular Signalling, 11(1), 15-23. https://doi.org/10.1016/S0898-6568(98)00024-2