MAPK and PI3K activities are required for leptin stimulation of protein synthesis in human trophoblastic cells

Leptin, the LEP gene product, is produced in placenta where it has been found to be an important autocrine signal for trophoblastic growth during pregnancy. Thus, we have recently described the antiapoptotic and trophic effect of leptin on choriocarcinoma cell line JEG-3, stimulating DNA and protein...

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Autores principales:	Pérez-Pérez, A., Gambino, Y., Maymó, J., Goberna, R., Fabiani, F., Varone, C., Sánchez-Margalet, V.
Formato:	JOUR
Materias:	Leptin Placenta Protein synthesis Signal transduction Translation DNA initiation factor 4E initiation factor 4E binding protein 1 Janus kinase leptin leptin receptor leucine mitogen activated protein kinase phosphatidylinositol 3 kinase protein kinase B S6 kinase STAT protein tritium apoptosis article autocrine effect cell growth choriocarcinoma controlled study DNA synthesis enzyme activation enzyme activity enzyme inhibition genetic transfection human human cell pregnancy priority journal protein phosphorylation protein synthesis protein synthesis inhibition protein synthesis regulation signal transduction translation initiation trophoblast 1-Phosphatidylinositol 3-Kinase Adaptor Proteins, Signal Transducing Cell Line, Tumor Eukaryotic Initiation Factor-4E Female Humans MAP Kinase Signaling System Mitogen-Activated Protein Kinase Kinases Phosphoproteins Phosphorylation Pregnancy Protein Biosynthesis Proto-Oncogene Proteins c-akt Ribosomal Protein S6 Kinases, 70-kDa Trophoblasts
Acceso en línea:	http://hdl.handle.net/20.500.12110/paper_0006291X_v396_n4_p956_PerezPerez
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

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spelling	todo:paper_0006291X_v396_n4_p956_PerezPerez2023-10-03T14:03:58Z MAPK and PI3K activities are required for leptin stimulation of protein synthesis in human trophoblastic cells Pérez-Pérez, A. Gambino, Y. Maymó, J. Goberna, R. Fabiani, F. Varone, C. Sánchez-Margalet, V. Leptin Placenta Protein synthesis Signal transduction Translation DNA initiation factor 4E initiation factor 4E binding protein 1 Janus kinase leptin leptin receptor leucine mitogen activated protein kinase phosphatidylinositol 3 kinase protein kinase B S6 kinase STAT protein tritium apoptosis article autocrine effect cell growth choriocarcinoma controlled study DNA synthesis enzyme activation enzyme activity enzyme inhibition genetic transfection human human cell pregnancy priority journal protein phosphorylation protein synthesis protein synthesis inhibition protein synthesis regulation signal transduction translation initiation trophoblast 1-Phosphatidylinositol 3-Kinase Adaptor Proteins, Signal Transducing Cell Line, Tumor Eukaryotic Initiation Factor-4E Female Humans Leptin MAP Kinase Signaling System Mitogen-Activated Protein Kinase Kinases Phosphoproteins Phosphorylation Pregnancy Protein Biosynthesis Proto-Oncogene Proteins c-akt Ribosomal Protein S6 Kinases, 70-kDa Trophoblasts Leptin, the LEP gene product, is produced in placenta where it has been found to be an important autocrine signal for trophoblastic growth during pregnancy. Thus, we have recently described the antiapoptotic and trophic effect of leptin on choriocarcinoma cell line JEG-3, stimulating DNA and protein synthesis. We have also demonstrated the presence of leptin receptor and leptin signaling in normal human trophoblastic cells, activating JAK-STAT, PI3K and MAPK pathways. In the present work we have employed dominant negative forms of MAPK and PKB constructs to find out the signaling pathways that specifically mediates the effect of leptin on protein synthesis. As previously shown, leptin stimulates protein synthesis as assessed by 3 H-leucine incorporation. However, both dominant negative forms of MAPK and PKB inhibited protein synthesis in JEG-3 choriocarcinoma cells. The inhibition of PKB and MAPK activity by transfection with the dominant negative kinases prevented the leptin stimulation of p70 S6K, which is known to be an important kinase in the regulation of protein synthesis. Moreover, leptin stimulation of phosphorylation of EIF4EBP1 and EIF4E, which allows the initiation of translation was also prevented by MAPK and PI3K dominant negative constructs. Therefore, these results demonstrate that both PI3K and MAPK are necessary to observe the effect of leptin signaling that mediates protein synthesis in choriocarcinoma cells JEG-3. © 2010 Elsevier Inc. All rights reserved. Fil:Gambino, Y. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Maymó, J. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Varone, C. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_0006291X_v396_n4_p956_PerezPerez
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	Leptin Placenta Protein synthesis Signal transduction Translation DNA initiation factor 4E initiation factor 4E binding protein 1 Janus kinase leptin leptin receptor leucine mitogen activated protein kinase phosphatidylinositol 3 kinase protein kinase B S6 kinase STAT protein tritium apoptosis article autocrine effect cell growth choriocarcinoma controlled study DNA synthesis enzyme activation enzyme activity enzyme inhibition genetic transfection human human cell pregnancy priority journal protein phosphorylation protein synthesis protein synthesis inhibition protein synthesis regulation signal transduction translation initiation trophoblast 1-Phosphatidylinositol 3-Kinase Adaptor Proteins, Signal Transducing Cell Line, Tumor Eukaryotic Initiation Factor-4E Female Humans Leptin MAP Kinase Signaling System Mitogen-Activated Protein Kinase Kinases Phosphoproteins Phosphorylation Pregnancy Protein Biosynthesis Proto-Oncogene Proteins c-akt Ribosomal Protein S6 Kinases, 70-kDa Trophoblasts
spellingShingle	Leptin Placenta Protein synthesis Signal transduction Translation DNA initiation factor 4E initiation factor 4E binding protein 1 Janus kinase leptin leptin receptor leucine mitogen activated protein kinase phosphatidylinositol 3 kinase protein kinase B S6 kinase STAT protein tritium apoptosis article autocrine effect cell growth choriocarcinoma controlled study DNA synthesis enzyme activation enzyme activity enzyme inhibition genetic transfection human human cell pregnancy priority journal protein phosphorylation protein synthesis protein synthesis inhibition protein synthesis regulation signal transduction translation initiation trophoblast 1-Phosphatidylinositol 3-Kinase Adaptor Proteins, Signal Transducing Cell Line, Tumor Eukaryotic Initiation Factor-4E Female Humans Leptin MAP Kinase Signaling System Mitogen-Activated Protein Kinase Kinases Phosphoproteins Phosphorylation Pregnancy Protein Biosynthesis Proto-Oncogene Proteins c-akt Ribosomal Protein S6 Kinases, 70-kDa Trophoblasts Pérez-Pérez, A. Gambino, Y. Maymó, J. Goberna, R. Fabiani, F. Varone, C. Sánchez-Margalet, V. MAPK and PI3K activities are required for leptin stimulation of protein synthesis in human trophoblastic cells
topic_facet	Leptin Placenta Protein synthesis Signal transduction Translation DNA initiation factor 4E initiation factor 4E binding protein 1 Janus kinase leptin leptin receptor leucine mitogen activated protein kinase phosphatidylinositol 3 kinase protein kinase B S6 kinase STAT protein tritium apoptosis article autocrine effect cell growth choriocarcinoma controlled study DNA synthesis enzyme activation enzyme activity enzyme inhibition genetic transfection human human cell pregnancy priority journal protein phosphorylation protein synthesis protein synthesis inhibition protein synthesis regulation signal transduction translation initiation trophoblast 1-Phosphatidylinositol 3-Kinase Adaptor Proteins, Signal Transducing Cell Line, Tumor Eukaryotic Initiation Factor-4E Female Humans Leptin MAP Kinase Signaling System Mitogen-Activated Protein Kinase Kinases Phosphoproteins Phosphorylation Pregnancy Protein Biosynthesis Proto-Oncogene Proteins c-akt Ribosomal Protein S6 Kinases, 70-kDa Trophoblasts
description	Leptin, the LEP gene product, is produced in placenta where it has been found to be an important autocrine signal for trophoblastic growth during pregnancy. Thus, we have recently described the antiapoptotic and trophic effect of leptin on choriocarcinoma cell line JEG-3, stimulating DNA and protein synthesis. We have also demonstrated the presence of leptin receptor and leptin signaling in normal human trophoblastic cells, activating JAK-STAT, PI3K and MAPK pathways. In the present work we have employed dominant negative forms of MAPK and PKB constructs to find out the signaling pathways that specifically mediates the effect of leptin on protein synthesis. As previously shown, leptin stimulates protein synthesis as assessed by 3 H-leucine incorporation. However, both dominant negative forms of MAPK and PKB inhibited protein synthesis in JEG-3 choriocarcinoma cells. The inhibition of PKB and MAPK activity by transfection with the dominant negative kinases prevented the leptin stimulation of p70 S6K, which is known to be an important kinase in the regulation of protein synthesis. Moreover, leptin stimulation of phosphorylation of EIF4EBP1 and EIF4E, which allows the initiation of translation was also prevented by MAPK and PI3K dominant negative constructs. Therefore, these results demonstrate that both PI3K and MAPK are necessary to observe the effect of leptin signaling that mediates protein synthesis in choriocarcinoma cells JEG-3. © 2010 Elsevier Inc. All rights reserved.
format	JOUR
author	Pérez-Pérez, A. Gambino, Y. Maymó, J. Goberna, R. Fabiani, F. Varone, C. Sánchez-Margalet, V.
author_facet	Pérez-Pérez, A. Gambino, Y. Maymó, J. Goberna, R. Fabiani, F. Varone, C. Sánchez-Margalet, V.
author_sort	Pérez-Pérez, A.
title	MAPK and PI3K activities are required for leptin stimulation of protein synthesis in human trophoblastic cells
title_short	MAPK and PI3K activities are required for leptin stimulation of protein synthesis in human trophoblastic cells
title_full	MAPK and PI3K activities are required for leptin stimulation of protein synthesis in human trophoblastic cells
title_fullStr	MAPK and PI3K activities are required for leptin stimulation of protein synthesis in human trophoblastic cells
title_full_unstemmed	MAPK and PI3K activities are required for leptin stimulation of protein synthesis in human trophoblastic cells
title_sort	mapk and pi3k activities are required for leptin stimulation of protein synthesis in human trophoblastic cells
url	http://hdl.handle.net/20.500.12110/paper_0006291X_v396_n4_p956_PerezPerez
work_keys_str_mv	AT perezpereza mapkandpi3kactivitiesarerequiredforleptinstimulationofproteinsynthesisinhumantrophoblasticcells AT gambinoy mapkandpi3kactivitiesarerequiredforleptinstimulationofproteinsynthesisinhumantrophoblasticcells AT maymoj mapkandpi3kactivitiesarerequiredforleptinstimulationofproteinsynthesisinhumantrophoblasticcells AT gobernar mapkandpi3kactivitiesarerequiredforleptinstimulationofproteinsynthesisinhumantrophoblasticcells AT fabianif mapkandpi3kactivitiesarerequiredforleptinstimulationofproteinsynthesisinhumantrophoblasticcells AT varonec mapkandpi3kactivitiesarerequiredforleptinstimulationofproteinsynthesisinhumantrophoblasticcells AT sanchezmargaletv mapkandpi3kactivitiesarerequiredforleptinstimulationofproteinsynthesisinhumantrophoblasticcells
_version_	1807323871295045632

MAPK and PI3K activities are required for leptin stimulation of protein synthesis in human trophoblastic cells

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