IRS-4 mediated mitogenic signalling by insulin and growth hormone in LB cells, a murine T-cell lymphoma devoid of IGF-I receptors
| Autor: | Birgitte Ursø, Patricia A. Holst, Hans Tornqvist, David Naor, M. Mapoko Ilondo, Sophie Giorgetti, Claus T. Christoffersen, Margriet Ouwens, E Van Obberghen, Pierre De Meyts |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
medicine.medical_specialty
Insulin Receptor Substrate Proteins medicine.medical_treatment P70-S6 Kinase 1 Lymphoma T-Cell Receptor IGF Type 1 Mice Phosphatidylinositol 3-Kinases chemistry.chemical_compound Internal medicine Insulin receptor substrate Tumor Cells Cultured medicine Animals Humans Insulin Phosphorylation Receptor Adaptor Proteins Signal Transducing Phosphoinositide-3 Kinase Inhibitors Mice Inbred BALB C biology Tyrosine phosphorylation Cell Biology Phosphoproteins Enzyme Activation Insulin receptor Endocrinology chemistry Growth Hormone biology.protein Tyrosine Cattle Female Mitogens Signal transduction Signal Transduction |
| Zdroj: | Cellular Signalling. 15:385-394 |
| ISSN: | 0898-6568 |
| Popis: | Insulin and growth hormone (GH) induce mitogenic and metabolic signals in cells, GH either directly or indirectly via IGF-I production. We have studied a spontaneous murine T-cell lymphoma (LB cells) devoid of IGF-1 receptors in which proliferation is maintained by insulin [Int. J. Cancer 50 (1992) 80], and show that GH is more potent than insulin, with both GH and insulin dose-response curves for thymidine incorporation being bell-shaped. Binding showed somatogenic rather than lactogenic GH receptors. Insulin stimulated phosphorylation of the insulin receptor and of a 160-kDa protein, identified as the IRS-4 protein. This phosphorylated IRS-4 associated with PI3-kinase, which was activated along with the downstream p70(S6) kinase, whereas the Ras-MAPK pathway was not. Using selective inhibitors, the PI3-kinase, but not p70(S6) kinase or MEK, was found to be involved in insulin-stimulated DNA synthesis. GH induced tyrosine phosphorylation of IRS-4 and nuclear translocation of STAT5. The LB cells constitute a new model for studying GH and insulin signalling without interference of IGF-1 receptors. |
| Databáze: | OpenAIRE |
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