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 language | English (US) |
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Pages (from-to) | 15-23 |
Number of pages | 9 |
Journal | Cellular Signalling |
Volume | 11 |
Issue number | 1 |
DOIs | |
State | Published - Jan 1999 |
Keywords
- Apoptosis
- Caspase-3
- Insulin
- Phosphatidylinositol 3'-kinase
- Signal transduction
- c-Jun N-terminal kinase
ASJC Scopus subject areas
- Cell Biology