RHO PREVENTS APOPTOSIS THROUGH BCL-2 EXPRESSION - IMPLICATIONS FOR INTERLEUKIN-2 RECEPTOR SIGNAL-TRANSDUCTION

Here we describe a Rho-mediated apoptosis suppression pathway driven b y 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 express ion through RhoA activation which is inhibited by the specific Rho fam ily inhibitor, Clostridium difficile Toxin B, as well as by a dominant negative RhoA mutant. Using transient transfections of RhoA mutants t agged with the vesicular stomatitis virus glycoprotein, we show that a constitutively active RhoA mutant induces Bcl-2 expression and preven ts apoptosis upon IL-4 withdrawal. Finally we have identified the sign aling pathway involved together with RhoA in Bcl-2 induction and show compelling evidence for the implication of phosphatidylinositol 3 kina se and protein kinase C.