ROLE OF P70 S6 KINASE IN CYTOKINE-REGULATED HEMATOPOIETIC-CELL SURVIVAL

The signalling mechanisms required for cell survival remain relatively undefined. We and others have shown that phosphatidylinositol 3-kinas e (PI 3-kinase) is an important enzyme in the prevention of apoptosis, and this property is independent of p21(ras) - MAP kinase activation. It is therefore important to define the downstream targets of this en zyme mediating the inhibition of apoptosis. We report here that p70 S6 kinase, a protein critical for progression through the cell cycle and a downstream effector of PI 3-kinase, is not required for the surviva l of cytokine-stimulated human T-cells or murine mast cells. The poten t inhibitor of p70 S6 kinase activation, rapamycin, was unable to indu ce apoptosis in cells stimulated with cytokines. As well, PI 3-kinase inhibitors that also blocked the activation of p70 S6 kinase were able to induce apoptosis. These studies, therefore, describe a bifurcation of signalling pathways from PI 3-kinase leading to different physiolo gical outcomes.