The phosphatidylinositol 3-kinase/Akt signaling pathway modulates the endocrine differentiation of trophoblast cells
| Autor: | Takayuki Kamei, Kerry L. McGonigle, Belinda M. Chapman, Stephanie R. Jones, Michael J. Soares, Guoli Dai |
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| Rok vydání: | 2002 |
| Předmět: |
Fetal Proteins
Morpholines Endocrine System Protein Serine-Threonine Kinases Receptor tyrosine kinase src Homology Domains Mice Phosphatidylinositol 3-Kinases Endocrinology LYN Proto-Oncogene Proteins Animals Receptor Fibroblast Growth Factor Type 1 Enzyme Inhibitors Phosphorylation Molecular Biology Protein kinase B PI3K/AKT/mTOR pathway Phosphoinositide-3 Kinase Inhibitors biology Akt/PKB signaling pathway JAK-STAT signaling pathway Receptor Protein-Tyrosine Kinases Cell Differentiation General Medicine Receptors Fibroblast Growth Factor Trophoblast giant cell differentiation Cell biology Rats Trophoblasts src-Family Kinases Chromones embryonic structures Cancer research biology.protein Female biological phenomena cell phenomena and immunity Proto-Oncogene Proteins c-akt Cell Division Proto-oncogene tyrosine-protein kinase Src Signal Transduction |
| Zdroj: | Molecular endocrinology (Baltimore, Md.). 16(7) |
| ISSN: | 0888-8809 |
| Popis: | Activation of Lyn, a Src-related nonreceptor tyrosine kinase, in trophoblast cells is associated with trophoblast giant cell differentiation. The purpose of the present work was to use Lyn as a tool to identify signaling pathways regulating the endocrine differentiation of trophoblast cells. The Src homology 3 domain of Lyn was shown to display differentiation-dependent associations with other regulatory proteins, including phosphatidylinositol 3-kinase (PI3-K). PI3-K activation was dependent upon trophoblast giant cell differentiation. The downstream mediator of PI3-K, Akt/protein kinase B, also exhibited differentiation-dependent activation. Lyn is a potential regulator of the PI3-K/Akt signaling pathway, as are receptor tyrosine kinases. Protein tyrosine kinase profiling was used to identify two candidate regulators of the PI3-K/Akt pathway, fibroblast growth factor receptor-1 and Sky. At least part of the activation of Akt in differentiating trophoblast giant cells involves an autocrine growth arrestspecific-6-Sky signaling pathway. Inhibition of PI3-K activities via treatment with LY294002 disrupted Akt activation and interfered with the endocrine differentiation of trophoblast giant cells. In summary, activation of the PI3-K/Akt signaling pathway regulates the development of the differentiated trophoblast giant cell phenotype. (Molecular Endocrinology 16: 1469–1481, 2002) |
| Databáze: | OpenAIRE |
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