Insulin-like growth factor I receptor signaling in differentiation of neuronal H19-7 cells
| Autor: | A, Morrione, G, Romano, M, Navarro, K, Reiss, B, Valentinis, M, Dews, E, Eves, M R, Rosner, R, Baserga |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Src Homology 2 Domain-Containing
Transforming Protein 1 MAP Kinase Signaling System Hippocampus Cell Line Receptor IGF Type 1 Mice Phosphatidylinositol 3-Kinases Animals Humans Insulin-Like Growth Factor I Phosphorylation Adaptor Proteins Signal Transducing Phosphoinositide-3 Kinase Inhibitors Mitogen-Activated Protein Kinase Kinases Neurons Temperature Proteins Cell Differentiation Fibroblasts Phosphoproteins Rats Enzyme Activation Adaptor Proteins Vesicular Transport Amino Acid Substitution Shc Signaling Adaptor Proteins Mutation Insulin Receptor Substrate Proteins Mitogen-Activated Protein Kinases Cell Division |
| Zdroj: | Cancer research. 60(8) |
| ISSN: | 0008-5472 1280-1283 |
| Popis: | The type I insulin-like growth factor receptor (IGF-IR) is known to send two seemingly contradictory signals inducing either cell proliferation or cell differentiation, depending on cell type and/or conditions. H19-7 cells are rat hippocampal neuronal cells immortalized by a temperature-sensitive SV40 large T antigen that grow at 34 degrees C in epidermal growth factor or serum but differentiate at 39 degrees C when induced by basic fibroblast growth factor. At 39 degrees C, expression of the human IGF-IR in H19-7 cells induces an insulin-like growth factor (IGF) I-dependent differentiation. We have investigated the domains of the IGF-IR required for differentiation of H19-7 cells. The tyrosine 950 residue and serines 1280-1283 in the COOH terminus of the receptor are required for IGF-I-induced differentiation at 39 degrees C, although they are dispensable for IGF-I-mediated growth at 34 degrees C. Both domains have to be mutated to inactivate the differentiating function. The inability of these mutant receptors to induce differentiation correlates with mitogen-activated protein kinase activation. In contrast, inhibitors of phosphatidylinositol 3'-kinase have no effect on IGF-I-mediated differentiation of H19-7 cells, although they do inhibit the mitogenic response. |
| Databáze: | OpenAIRE |
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