Background: Phosphatidylinositol 3-kinase (PI3K) is necessary for insulin action on glucose and lipid metabolism. In epithelial cells, which do not express GLUT4 and gluconeogenic enzymes, insulin mediated PI3K activation regulates cell survival, growth, proliferation and motility. Although the involvement of p85αregulatory subunit of PI3K (p85αPI3K) in insulin signal transduction has been extensively studied, the function of the N-terminus of p85αPI3K remains elusive. A serine at codon 83 (S83) in the p85αPI3K that is phosphorylated by protein kinase A (PKA) invivo and in vitrohas been identified. Methods: To determine the molecular mechanism linking PKA to insulin mediated PI3K activation in MCF7 cells, we used p85αPI3K mutated forms, in which S83 has been substituted with alanine (p85A) to prevent phosphorylation or with aspartic acid (p85D) to mimic the phosphorylated residue. Results: We demonstrated that phosphorylation of p85αPI3KS83 modulates the formation of the p85αPI3K/IRS1 complex and its subcellular localization influencing the kinetics of the insulin signaling both on MAPK-ERK and AKT pathways. Growth curves and cell cycle analysis demonstrated that phosphorylation of p85αPI3KS83 plays a central role in the control of insulin mediated cell proliferation. Conclusions:In conclusion, the insulin-modulated plating efficiency and cell migration were markedly influenced by the expression of the p85αPI3KS83 mutants.

The p85 Regulatory Subunit of PI3K Mediates cAMP–PKA and Insulin Biological Effects on MCF-7 Cell Growth and Motility / Di Domenico, M; Feola, Antonia; Di Zazzo, E; Zuchegna, Candida; Romano, Antonella; Porcellini, Antonio. - In: THE AMERICAN JOURNAL OF PATHOLOGY. - ISSN 0002-9440. - 184:9(2014), pp. S17-S17. [10.1016/S0002-9440(14)00477-5]

The p85 Regulatory Subunit of PI3K Mediates cAMP–PKA and Insulin Biological Effects on MCF-7 Cell Growth and Motility.

FEOLA, ANTONIA;ZUCHEGNA, CANDIDA;ROMANO, ANTONELLA;PORCELLINI, ANTONIO
2014

Abstract

Background: Phosphatidylinositol 3-kinase (PI3K) is necessary for insulin action on glucose and lipid metabolism. In epithelial cells, which do not express GLUT4 and gluconeogenic enzymes, insulin mediated PI3K activation regulates cell survival, growth, proliferation and motility. Although the involvement of p85αregulatory subunit of PI3K (p85αPI3K) in insulin signal transduction has been extensively studied, the function of the N-terminus of p85αPI3K remains elusive. A serine at codon 83 (S83) in the p85αPI3K that is phosphorylated by protein kinase A (PKA) invivo and in vitrohas been identified. Methods: To determine the molecular mechanism linking PKA to insulin mediated PI3K activation in MCF7 cells, we used p85αPI3K mutated forms, in which S83 has been substituted with alanine (p85A) to prevent phosphorylation or with aspartic acid (p85D) to mimic the phosphorylated residue. Results: We demonstrated that phosphorylation of p85αPI3KS83 modulates the formation of the p85αPI3K/IRS1 complex and its subcellular localization influencing the kinetics of the insulin signaling both on MAPK-ERK and AKT pathways. Growth curves and cell cycle analysis demonstrated that phosphorylation of p85αPI3KS83 plays a central role in the control of insulin mediated cell proliferation. Conclusions:In conclusion, the insulin-modulated plating efficiency and cell migration were markedly influenced by the expression of the p85αPI3KS83 mutants.
2014
The p85 Regulatory Subunit of PI3K Mediates cAMP–PKA and Insulin Biological Effects on MCF-7 Cell Growth and Motility / Di Domenico, M; Feola, Antonia; Di Zazzo, E; Zuchegna, Candida; Romano, Antonella; Porcellini, Antonio. - In: THE AMERICAN JOURNAL OF PATHOLOGY. - ISSN 0002-9440. - 184:9(2014), pp. S17-S17. [10.1016/S0002-9440(14)00477-5]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/610786
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