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

Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire
M P ScheidV Duronio

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 than 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.

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Citations

Jun 24, 1998·Proceedings of the National Academy of Sciences of the United States of America·M P Scheid, V Duronio
Apr 29, 2005·Brain Research. Molecular Brain Research·Wen-Lin AnRichard F Cowburn
Jun 11, 2002·Biochemical and Biophysical Research Communications·Jason A Lehman, Julian Gomez-Cambronero
May 9, 2012·Expert Opinion on Therapeutic Targets·Carman K M Ip, Alice S T Wong
Jun 18, 2002·Journal of Cellular and Molecular Medicine·M J Clemens
Oct 8, 2003·Experimental Biology and Medicine·Suwannee UthaisangsookSoichi Haraguchi
Oct 2, 2020·International Journal of Molecular Sciences·Jinhong MengJennifer E Morgan

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