Rho prevents apoptosis through Bcl-2 expression: implications for interleukin-2 receptor signal transduction.
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.
Gómez
J
J
Department of Immunology and Oncology, Centro Nacional de Biotecnología-CSIC, Universidad Autónoma, Madrid, Spain.
Martínez
C
C
Giry
M
M
García
A
A
Rebollo
A
A
D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D015536:Down-Regulation / Q000276:immunology; D019204:GTP-Binding Proteins / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007376:Interleukin-2 / Q000172:deficiency; D051379:Mice; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis* / Q000187:drug effects; D015375:Receptors, Interleukin-2 / Q000502:physiology*; D015398:Signal Transduction / Q000276:immunology*; D014162:Transfection / Q000276:immunology; D020742:rhoA GTP-Binding Protein
D007376:Interleukin-2; D019253:Proto-Oncogene Proteins c-bcl-2; D015375:Receptors, Interleukin-2; D019869:Phosphatidylinositol 3-Kinases; D011493:Protein Kinase C; D019204:GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein