Abstract
Here we describe a Rho-mediated apoptosis suppression pathway driven by Bcl-2 expression in the interleukin (IL)-4- or IL-2-dependent murine T cell line TS1 alpha beta. IL-2, but not IL-4, induces Bcl-2 expression through RhoA activation which is inhibited by the specific Rho family inhibitor, Clostridium difficile Toxin B, as well as by a dominant negative RhoA mutant. Using transient transfections of RhoA mutants tagged with the vesicular stomatitis virus glycoprotein, we show that a constitutively active RhoA mutant induces Bcl-2 expression and prevents apoptosis upon IL-4 withdrawal. Finally, we have identified the signaling pathway involved together with RhoA in Bcl-2 induction and show compelling evidence for the implication of phosphatidylinositol 3 kinase and protein kinase C.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Apoptosis / genetics
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Apoptosis / immunology
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Cell Line
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Down-Regulation / immunology
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GTP-Binding Proteins / genetics
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GTP-Binding Proteins / physiology*
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Humans
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Interleukin-2 / deficiency
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Mice
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Phosphatidylinositol 3-Kinases / metabolism
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Phosphatidylinositol 3-Kinases / pharmacology
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Protein Kinase C / metabolism
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Protein Kinase C / pharmacology
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Proto-Oncogene Proteins c-bcl-2 / biosynthesis*
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Proto-Oncogene Proteins c-bcl-2 / drug effects
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Receptors, Interleukin-2 / physiology*
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Signal Transduction / immunology*
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Transfection / immunology
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rhoA GTP-Binding Protein
Substances
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Interleukin-2
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Proto-Oncogene Proteins c-bcl-2
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Receptors, Interleukin-2
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Phosphatidylinositol 3-Kinases
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Protein Kinase C
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GTP-Binding Proteins
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rhoA GTP-Binding Protein