Abstract
The tumor suppressor gene PTEN encodes a 55-kDa enzyme that hydrolyzes both protein phosphotyrosyl and 3-phosphorylated inositol phospholipids in vitro. We have found that the latter activity is physiologically relevant in intact T cells. Expression of active PTEN lead to a 50% loss of transfected cells due to increased apoptosis, which was completely prevented by coexpression of a constitutively active, membrane-bound form of protein kinase B. A mutant of PTEN selectively lacking lipid phosphatase activity, but retaining protein phosphatase activity, had no effects on cell number. Active (but not mutant) PTEN also decreased TCR-induced activation of the mitogen-activated protein kinase ERK2 (extracellular signal-related kinase 2), as seen after inhibition of phosphatidylinositol 3-kinase. Our data indicate that PTEN is a phosphatidylinositol 3-phosphatase in T cells, and we suggest that PTEN may play a role in the regulation of T cell survival and TCR signaling by directly opposing phosphatidylinositol 3-kinase.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Apoptosis / immunology
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CD3 Complex / immunology
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Cell Survival / immunology
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Enzyme Activation / immunology
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Enzyme Inhibitors / pharmacology
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Genes, Tumor Suppressor*
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Humans
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Jurkat Cells
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Mitogen-Activated Protein Kinase 1 / antagonists & inhibitors
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Mitogen-Activated Protein Kinase 1 / metabolism
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Mitogen-Activated Protein Kinases / antagonists & inhibitors
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Mitogen-Activated Protein Kinases / metabolism
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Myristic Acid / metabolism
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PTEN Phosphohydrolase
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Phosphoric Monoester Hydrolases / biosynthesis
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Phosphoric Monoester Hydrolases / genetics
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Phosphoric Monoester Hydrolases / metabolism*
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Phosphoric Monoester Hydrolases / physiology*
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Phosphorylation
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Protein Serine-Threonine Kinases*
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Proto-Oncogene Proteins / metabolism
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Proto-Oncogene Proteins c-akt
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Receptors, Antigen, T-Cell / antagonists & inhibitors
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Receptors, Antigen, T-Cell / metabolism*
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Receptors, Antigen, T-Cell / physiology
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Signal Transduction / immunology*
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T-Lymphocytes / cytology*
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T-Lymphocytes / metabolism
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Tumor Suppressor Proteins*
Substances
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CD3 Complex
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Enzyme Inhibitors
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Proto-Oncogene Proteins
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Receptors, Antigen, T-Cell
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Tumor Suppressor Proteins
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Myristic Acid
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Protein Serine-Threonine Kinases
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Proto-Oncogene Proteins c-akt
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Mitogen-Activated Protein Kinase 1
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Mitogen-Activated Protein Kinases
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Phosphoric Monoester Hydrolases
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phosphatidylinositol-3-phosphatase
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PTEN Phosphohydrolase
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PTEN protein, human