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PI3K–Akt signaling controls PFKFB3 expression during human T-lymphocyte activation
by
Fontova, Pere
, Manzano, Anna
, Rodríguez-García, Ana
, Arnedo-Pac, Claudia
, Simon-Molas, Helga
, Bartrons, Ramon
, Vidal-Alabró, Anna
, Navarro-Sabaté, Àurea
, Lloberas, Núria
, Castaño, Esther
in
1-Phosphatidylinositol 3-kinase
/ 6-Phosphofructo-2-kinase
/ AKT protein
/ Analysis
/ Antigens
/ Biochemistry
/ Biomedical and Life Sciences
/ Cardiology
/ Cell activation
/ Cell culture
/ Cell proliferation
/ Enzymes
/ Fructose
/ Gene expression
/ Glycolysis
/ Human behavior
/ Immune response
/ Immune system
/ Inhibitors
/ Kinases
/ Lactates
/ Lactic acid
/ Life Sciences
/ Lymphocyte receptors
/ Lymphocytes
/ Lymphocytes T
/ Medical Biochemistry
/ Metabolism
/ Mitogens
/ Molecular modelling
/ Oncology
/ Proliferating cell nuclear antigen
/ Signal transduction
/ Signaling
/ T cell receptors
/ T cells
2018
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PI3K–Akt signaling controls PFKFB3 expression during human T-lymphocyte activation
by
Fontova, Pere
, Manzano, Anna
, Rodríguez-García, Ana
, Arnedo-Pac, Claudia
, Simon-Molas, Helga
, Bartrons, Ramon
, Vidal-Alabró, Anna
, Navarro-Sabaté, Àurea
, Lloberas, Núria
, Castaño, Esther
in
1-Phosphatidylinositol 3-kinase
/ 6-Phosphofructo-2-kinase
/ AKT protein
/ Analysis
/ Antigens
/ Biochemistry
/ Biomedical and Life Sciences
/ Cardiology
/ Cell activation
/ Cell culture
/ Cell proliferation
/ Enzymes
/ Fructose
/ Gene expression
/ Glycolysis
/ Human behavior
/ Immune response
/ Immune system
/ Inhibitors
/ Kinases
/ Lactates
/ Lactic acid
/ Life Sciences
/ Lymphocyte receptors
/ Lymphocytes
/ Lymphocytes T
/ Medical Biochemistry
/ Metabolism
/ Mitogens
/ Molecular modelling
/ Oncology
/ Proliferating cell nuclear antigen
/ Signal transduction
/ Signaling
/ T cell receptors
/ T cells
2018
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PI3K–Akt signaling controls PFKFB3 expression during human T-lymphocyte activation
by
Fontova, Pere
, Manzano, Anna
, Rodríguez-García, Ana
, Arnedo-Pac, Claudia
, Simon-Molas, Helga
, Bartrons, Ramon
, Vidal-Alabró, Anna
, Navarro-Sabaté, Àurea
, Lloberas, Núria
, Castaño, Esther
in
1-Phosphatidylinositol 3-kinase
/ 6-Phosphofructo-2-kinase
/ AKT protein
/ Analysis
/ Antigens
/ Biochemistry
/ Biomedical and Life Sciences
/ Cardiology
/ Cell activation
/ Cell culture
/ Cell proliferation
/ Enzymes
/ Fructose
/ Gene expression
/ Glycolysis
/ Human behavior
/ Immune response
/ Immune system
/ Inhibitors
/ Kinases
/ Lactates
/ Lactic acid
/ Life Sciences
/ Lymphocyte receptors
/ Lymphocytes
/ Lymphocytes T
/ Medical Biochemistry
/ Metabolism
/ Mitogens
/ Molecular modelling
/ Oncology
/ Proliferating cell nuclear antigen
/ Signal transduction
/ Signaling
/ T cell receptors
/ T cells
2018
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PI3K–Akt signaling controls PFKFB3 expression during human T-lymphocyte activation
Journal Article
PI3K–Akt signaling controls PFKFB3 expression during human T-lymphocyte activation
2018
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Overview
Lymphocyte activation is associated with rapid increase of both the glycolytic activator fructose 2,6-bisphosphate (Fru-2,6-P
2
) and the enzyme responsible for its synthesis, 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFK-2/FBPase-2). PFKFB3 gene, which encodes for the most abundant PFK-2 isoenzyme in proliferating tissues, has been found overexpressed during cell activation in several models, including immune cells. However, there is limited knowledge on the pathways underlying PFKFB3 regulation in human T-lymphocytes, and the role of this gene in human immune response. The aim of this work is to elucidate the molecular mechanisms of PFKFB3 induction during human T-lymphocyte activation by mitotic agents. The results obtained showed PFKFB3 induction during human T-lymphocyte activation by mitogens such as phytohemagglutinin (PHA). PFKFB3 increase occurred concomitantly with GLUT-1, HK-II, and PCNA upregulation, showing that mitotic agents induce a metabolic reprograming process that is required for T-cell proliferation. PI3K–Akt pathway inhibitors, Akti-1/2 and LY294002, reduced PFKFB3 gene induction by PHA, as well as Fru-2,6-P
2
and lactate production. Moreover, both inhibitors blocked activation and proliferation in response to PHA, showing the importance of PI3K/Akt signaling pathway in the antigen response of T-lymphocytes. These results provide a link between metabolism and T-cell antigen receptor signaling in human lymphocyte biology that can help to better understand the importance of modulating both pathways to target complex diseases involving the activation of the immune system.
Publisher
Springer US,Springer,Springer Nature B.V
Subject
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