Phosphatidylinositol 3-Kinase Inhibitors Block Aortic Smooth Muscle Cell Proliferation in Mid-Late G1 Phase: Effect on Cyclin-Dependent Kinase 2 and the Inhibitory Protein p27KIP1
| Autor: | Bertrand Perret, Monique Breton-Douillon, Daniel Bacqueville, Hugues Chap, Fabrice Casagrande, Jean-Marie Darbon |
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| Rok vydání: | 1998 |
| Předmět: |
Vascular smooth muscle
Swine Morpholines Biophysics Cell Cycle Proteins Protein Serine-Threonine Kinases Mitogen-activated protein kinase kinase Biochemistry Muscle Smooth Vascular Wortmannin chemistry.chemical_compound CDC2-CDC28 Kinases Animals Phosphatidylinositol Kinase activity Molecular Biology Aorta Phosphoinositide-3 Kinase Inhibitors Dose-Response Relationship Drug biology Akt/PKB signaling pathway Tumor Suppressor Proteins Cyclin-Dependent Kinase 2 Cyclin-dependent kinase 2 G1 Phase Cell Biology Molecular biology Cyclin-Dependent Kinases Cell biology Androstadienes chemistry Chromones biology.protein Microtubule-Associated Proteins cGMP-dependent protein kinase Cyclin-Dependent Kinase Inhibitor p27 |
| Zdroj: | Biochemical and Biophysical Research Communications. 244:630-636 |
| ISSN: | 0006-291X |
| DOI: | 10.1006/bbrc.1997.7885 |
| Popis: | In the present study, we investigated the involvement of phosphatidylinositol 3-kinase (PI 3-kinase) activity in the progression of vascular smooth muscle cells (VSMCs) throughout the G1 phase of cell cycle. Addition of two selective inhibitors of PI 3-kinase, LY 294002 or wortmannin, to quiescent VSMCs prevented serum-induced DNA synthesis in a dose-dependent manner with IC50 of 8.7 +/- 2.0 microM and 53.9 +/- 8.5 nM, respectively. Time course studies revealed that the two PI 3-kinase inhibitors blocked VSMC proliferation in mid-late G1 phase, about 6 h before the G1/S transition. This G1 growth arrest was due, at least in part, to the reduction of the CDK2 associated kinase activity resulting mainly from the upregulation of the inhibitory protein p27KIP1. |
| Databáze: | OpenAIRE |
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