Role of p70 S6 kinase in cytokine-regulated hemopoietic cell survival

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Abstract
The signalling mechanisms required for cell survival remain relatively undefined. We and others have shown that phosphatidylinositol 3-kinase (PI 3-kinase) is an important enzyme in the prevention of apoptosis, and this property is independent of p21ras– MAP kinase activation. It is therefore important to define the downstream targets of this enzyme 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 survival of cytokine-stimulated human T-cells or murine mast cells. The potent inhibitor of p70 S6 kinase activation, rapamycin, was unable to induce 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 physiological outcomes.Key words: p70 S6 kinase, phosphatidylinositol 3-kinase, apoptosis, cytokines, wortmannin.