Insulin and IGF-I receptors signaling in protection from apoptosis.
R-cells are mouse embryo fibroblasts with a targeted disruption of the insulin-like growth factor I receptor (IGF-IR) genes. Because R-cells do not express the IGF-IR, they are ideal for studying the biological effects of the insulin receptor (IR), independently from any contribution by the IGF-IR. By stably transfecting R-cells with constructs expressing the IR, we show here the IR can protect cells from apoptosis induced by anoikis or by okadaic acid. The IR, however, is not as efficient as the IGF-IR in protecting mouse embryo fibroblasts from apoptosis, even when IRS-1, one of its major substrates, is over-expressed. In addition, the protection by the IGF-IR is resistant to inhibitors of phosphatidylinositol 3-kinase (PI 3-ki), while the anti-apoptotic effect of the IR is sensitive. These experiments suggest that the IGF-IR uses an alternative anti-apoptotic pathway, not shared with the IR, which is PI3-ki-independent.
Prisco
M
M
Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA.
Romano
G
G
Peruzzi
F
F
Valentinis
B
B
Baserga
R
R
D016475:3T3 Cells / Q000737:chemistry / Q000166:cytology / Q000201:enzymology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002470:Cell Survival / Q000502:physiology; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic; D007328:Insulin / Q000502:physiology*; D007334:Insulin-Like Growth Factor I / Q000502:physiology; D051379:Mice; D019319:Okadaic Acid / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D011102:Polyhydroxyethyl Methacrylate / Q000494:pharmacology; D017526:Receptor, IGF Type 1 / Q000235:genetics*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D014162:Transfection; D014443:Tyrosine / Q000502:physiology
D016895:Culture Media, Serum-Free; D004791:Enzyme Inhibitors; D007328:Insulin; D019319:Okadaic Acid; D011102:Polyhydroxyethyl Methacrylate; D014443:Tyrosine; D007334:Insulin-Like Growth Factor I; D019869:Phosphatidylinositol 3-Kinases; D017526:Receptor, IGF Type 1; D017871:Calcium-Calmodulin-Dependent Protein Kinases