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.
References
Mar 1, 1992·Proceedings of the National Academy of Sciences of the United States of America·V DuronioJ W Schrader
Jun 26, 1992·Cell·J ChungJ Blenis
Aug 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·V CalvoB E Bierer
Aug 1, 1992·Proceedings of the National Academy of Sciences of the United States of America·S FerrariG Thomas
Jul 2, 1992·Nature·C J KuoG R Crabtree
Mar 1, 1991·Molecular and Cellular Biology·Y KoltinG P Livi
Nov 15, 1995·The Biochemical Journal·M P ScheidV Duronio
Sep 14, 1995·Nature·X J SunM F White
Jun 2, 1995·Cell·T F FrankeP N Tsichlis
Jun 6, 1995·Proceedings of the National Academy of Sciences of the United States of America·Q P WengJ Avruch
Jan 13, 1995·The Journal of Biological Chemistry·C J SabersR T Abraham
Jun 30, 1994·Nature·E J BrownS L Schreiber
Jul 7, 1994·Nature·J ChungJ Blenis
Aug 1, 1994·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·R Kapeller, L C Cantley
Dec 1, 1993·The Biochemical Journal·A Arcaro, M P Wymann
Dec 1, 1995·Current Opinion in Cell Biology·M M Chou, J Blenis
Citations
May 26, 2004·Leukemia Research·Julian Gomez-CambroneroMichael Baumann
Jul 21, 1998·Leukemia Research·C F BassøeA Vedeler
Jun 9, 1998·Cellular Signalling·V DuronioS Ettinger
May 23, 2001·The Biochemical Journal·K M Schubert, V Duronio
Apr 1, 1997·Immunology·J K JacksonH M Burt
Jun 24, 1998·Proceedings of the National Academy of Sciences of the United States of America·M P Scheid, V Duronio
Jun 14, 2000·Cytokine·M A AronicaM Boothby
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
Dec 1, 1998·Endocrinology·M BlázquezV L Trudeau
May 13, 2003·The Journal of Biological Chemistry·Jason A LehmanJulian Gomez-Cambronero
Oct 8, 2003·Experimental Biology and Medicine·Suwannee UthaisangsookSoichi Haraguchi
Oct 2, 2020·International Journal of Molecular Sciences·Jinhong MengJennifer E Morgan