The p85 Regulatory Subunit of PI3K Mediates cAMP-PKA and Insulin Biological Effects on MCF-7 Cell Growth and Motility
Recent studies have shown that hyperinsulinemia may increase the cancer risk. Moreover, many tumors demonstrate an increased activation of IR signaling pathways. Phosphatidylinositol 3-kinase (PI3K) is necessary for insulin action. In epithelial cells, which do not express GLUT4 and gluconeogenic en...
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2014-01-01
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| Series: | The Scientific World Journal |
| Online Access: | http://dx.doi.org/10.1155/2014/565839 |
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| author | E. Di Zazzo A. Feola C. Zuchegna A. Romano C. F. Donini S. Bartollino C. Costagliola R. Frunzio P. Laccetti M. Di Domenico A. Porcellini |
| author_facet | E. Di Zazzo A. Feola C. Zuchegna A. Romano C. F. Donini S. Bartollino C. Costagliola R. Frunzio P. Laccetti M. Di Domenico A. Porcellini |
| author_sort | E. Di Zazzo |
| collection | DOAJ |
| description | Recent studies have shown that hyperinsulinemia may increase the cancer risk. Moreover, many tumors demonstrate an increased activation of IR signaling pathways. Phosphatidylinositol 3-kinase (PI3K) is necessary for insulin action. In epithelial cells, which do not express GLUT4 and gluconeogenic enzymes, insulin-mediated PI3K activation regulates cell survival, growth, and motility. Although the involvement of the regulatory subunit of PI3K (p85αPI3K) in insulin signal transduction has been extensively studied, the function of its N-terminus remains elusive. It has been identified as a serine (S83) in the p85αPI3K that is phosphorylated by protein kinase A (PKA). To determine the molecular mechanism linking PKA to insulin-mediated PI3K activation, we used p85αPI3K mutated forms to prevent phosphorylation (p85A) or to mimic the phosphorylated residue (p85D). We demonstrated that phosphorylation of p85αPI3KS83 modulates the formation of the p85αPI3K/IRS-1 complex and its subcellular localization influencing the kinetics of the insulin signaling both on MAPK-ERK and AKT pathways. Furthermore, the p85αPI3KS83 phosphorylation plays a central role in the control of insulin-mediated cell proliferation, cell migration, and adhesion. This study highlights the p85αPI3KS83 role as a key regulator of cell proliferation and motility induced by insulin in MCF-7 cells breast cancer model. |
| format | Article |
| id | doaj-art-ed7dcad3f10a4268b337a26bf566bd22 |
| institution | Kabale University |
| issn | 2356-6140 1537-744X |
| language | English |
| publishDate | 2014-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | The Scientific World Journal |
| spelling | doaj-art-ed7dcad3f10a4268b337a26bf566bd222025-02-03T01:22:03ZengWileyThe Scientific World Journal2356-61401537-744X2014-01-01201410.1155/2014/565839565839The p85 Regulatory Subunit of PI3K Mediates cAMP-PKA and Insulin Biological Effects on MCF-7 Cell Growth and MotilityE. Di Zazzo0A. Feola1C. Zuchegna2A. Romano3C. F. Donini4S. Bartollino5C. Costagliola6R. Frunzio7P. Laccetti8M. Di Domenico9A. Porcellini10Department of Medicine and Health Sciences, University of Molise, Campobasso, ItalyDepartment of Biology, University Federico II of Naples, Naples, ItalyDepartment of Biology, University Federico II of Naples, Naples, ItalyDepartment of Biology, University Federico II of Naples, Naples, ItalyDepartment of Experimental Medicine, Sapienza University of Rome, Rome, ItalyDepartment of Medicine and Health Sciences, University of Molise, Campobasso, ItalyDepartment of Medicine and Health Sciences, University of Molise, Campobasso, ItalyDepartment of Biology, University Federico II of Naples, Naples, ItalyDepartment of Biology, University Federico II of Naples, Naples, ItalyDepartment of Biochemistry, Biophysics and General Pathology, Second University of Naples, ItalyDepartment of Biology, University Federico II of Naples, Naples, ItalyRecent studies have shown that hyperinsulinemia may increase the cancer risk. Moreover, many tumors demonstrate an increased activation of IR signaling pathways. Phosphatidylinositol 3-kinase (PI3K) is necessary for insulin action. In epithelial cells, which do not express GLUT4 and gluconeogenic enzymes, insulin-mediated PI3K activation regulates cell survival, growth, and motility. Although the involvement of the regulatory subunit of PI3K (p85αPI3K) in insulin signal transduction has been extensively studied, the function of its N-terminus remains elusive. It has been identified as a serine (S83) in the p85αPI3K that is phosphorylated by protein kinase A (PKA). To determine the molecular mechanism linking PKA to insulin-mediated PI3K activation, we used p85αPI3K mutated forms to prevent phosphorylation (p85A) or to mimic the phosphorylated residue (p85D). We demonstrated that phosphorylation of p85αPI3KS83 modulates the formation of the p85αPI3K/IRS-1 complex and its subcellular localization influencing the kinetics of the insulin signaling both on MAPK-ERK and AKT pathways. Furthermore, the p85αPI3KS83 phosphorylation plays a central role in the control of insulin-mediated cell proliferation, cell migration, and adhesion. This study highlights the p85αPI3KS83 role as a key regulator of cell proliferation and motility induced by insulin in MCF-7 cells breast cancer model.http://dx.doi.org/10.1155/2014/565839 |
| spellingShingle | E. Di Zazzo A. Feola C. Zuchegna A. Romano C. F. Donini S. Bartollino C. Costagliola R. Frunzio P. Laccetti M. Di Domenico A. Porcellini The p85 Regulatory Subunit of PI3K Mediates cAMP-PKA and Insulin Biological Effects on MCF-7 Cell Growth and Motility The Scientific World Journal |
| title | The p85 Regulatory Subunit of PI3K Mediates cAMP-PKA and Insulin Biological Effects on MCF-7 Cell Growth and Motility |
| title_full | The p85 Regulatory Subunit of PI3K Mediates cAMP-PKA and Insulin Biological Effects on MCF-7 Cell Growth and Motility |
| title_fullStr | The p85 Regulatory Subunit of PI3K Mediates cAMP-PKA and Insulin Biological Effects on MCF-7 Cell Growth and Motility |
| title_full_unstemmed | The p85 Regulatory Subunit of PI3K Mediates cAMP-PKA and Insulin Biological Effects on MCF-7 Cell Growth and Motility |
| title_short | The p85 Regulatory Subunit of PI3K Mediates cAMP-PKA and Insulin Biological Effects on MCF-7 Cell Growth and Motility |
| title_sort | p85 regulatory subunit of pi3k mediates camp pka and insulin biological effects on mcf 7 cell growth and motility |
| url | http://dx.doi.org/10.1155/2014/565839 |
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