R-Ras can activate the phosphoinositide 3-kinase but not the MAP kinase arm of the Ras effector pathways

Current Biology : CB
B M MarteJ Downward

Abstract

The small GTPase R-Ras displays a less potent transforming activity than the closely related Ras oncogene products. Although R-Ras has been reported to interact with c-Raf1 and Ral-GDS in vitro, the pathways by which it exerts its effects on cellular proliferation are not known. Both Ras and R-Ras interact with phosphoinositide (PI) 3-kinase in vitro, and induce elevation of the levels of PI 3-kinase lipid products in intact cells. Unlike Ras, R-Ras does not activate Raf or mitogen-activated protein (MAP) kinase in cells. In co-transfection assays, the serine/threonine protein kinase PKB (or Akt) is effectively stimulated by R-Ras, Ras, mutants of Ras that activate PI 3-kinase but not other effectors, and activated forms of PI 3-kinase. Ras and R-Ras stimulate PKB/Akt through a non-autocrine mechanism that involves PI 3-kinase. The constitutive activation of PI 3-kinase alone is sufficient to activate PKB/Akt, but not the MAP kinase ERK or the stress-activated protein kinase, Jun N-terminal kinase. Transformation assays in fibroblasts suggest that PKB/Akt and Raf are part of distinct oncogenic signalling pathways. Both the Raf-MAP kinase and PI 3-kinase-PKB/Akt pathways are activated by Ras, but only the PI 3-kinase-PKB/Akt pat...Continue Reading

References

May 15, 1991·Proceedings of the National Academy of Sciences of the United States of America·P F JonesB A Hemmings
Apr 1, 1990·Molecular and Cellular Biology·G T DrivasP D'Eustachio
Aug 1, 1987·Molecular and Cellular Biology·D G Lowe, D V Goeddel
Jul 1, 1984·Cell·F S Neuman-SilberbergB Z Shilo
Nov 7, 1995·Proceedings of the National Academy of Sciences of the United States of America·V AdlerZ Ronai
Aug 22, 1995·International Journal of Cancer. Journal International Du Cancer·A BellacosaJ R Testa
Dec 20, 1994·Proceedings of the National Academy of Sciences of the United States of America·M Spaargaren, J R Bischoff
Sep 1, 1994·Current Biology : CB·T KodakiP J Parker
Jun 1, 1994·The Biochemical Journal·M SpaargarenJ R Bischoff
Aug 18, 1994·Nature·P Rodriguez-VicianaJ Downward
Sep 13, 1994·Proceedings of the National Academy of Sciences of the United States of America·S RocheS A Courtneidge
Nov 18, 1993·Nature·M J Fernandez-Sarabia, J R Bischoff
Apr 5, 1996·Cell·Z ZhangE Ruoslahti
Apr 16, 1996·Proceedings of the National Academy of Sciences of the United States of America·J Q ChengJ R Testa
Sep 6, 1996·The Journal of Biological Chemistry·A D KohnR A Roth
Apr 1, 1996·Current Opinion in Cell Biology·C J Marshall
Aug 30, 1996·The Journal of Biological Chemistry·M L GalisteoJ Schlessinger

❮ Previous
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Citations

Jan 7, 2000·Journal of Cellular Physiology·S RokudaiT Tsuruo
Oct 18, 2002·Experimental Hematology·Annette EhrhardtJohn W Schrader
Dec 12, 1997·Biochimica Et Biophysica Acta·J L Bos
Apr 30, 1998·Current Opinion in Cell Biology·J Downward
Mar 14, 2000·Current Opinion in Cell Biology·G W Reuther, C J Der
Apr 8, 1998·Current Opinion in Genetics & Development·J Downward
Jan 11, 2001·Trends in Cardiovascular Medicine·P H Sugden, A Clerk
Oct 17, 2006·Nature Cell Biology·Mariam H OrmeSally J Leevers
Oct 23, 2003·Nature Reviews. Molecular Cell Biology·Kayoko KinbaraMark H Ginsberg
Jun 2, 2005·Nature Reviews. Neuroscience·Mary B KennedyLorraine R Washburn
Sep 22, 1999·European Journal of Biochemistry·S MasureA Richardson
Jul 22, 1998·Proceedings of the National Academy of Sciences of the United States of America·C P WebbG F Vande Woude
Nov 26, 1999·Proceedings of the National Academy of Sciences of the United States of America·J X ZouE Ruoslahti
Dec 28, 2006·The Journal of Experimental Medicine·Yan LiuWeiguo Zhang
Mar 18, 2005·Molecular Biology of the Cell·Stephen P HollyLeslie V Parise
Nov 5, 2004·Molecular Biology of the Cell·Michele A WozniakPatricia J Keely
Mar 9, 2007·Molecular Biology of the Cell·Akiyuki TakayaMichiyuki Matsuda
Jul 19, 2001·Journal of the National Cancer Institute·A A Adjei
Sep 16, 2004·Science's STKE : Signal Transduction Knowledge Environment·John Colicelli
May 15, 2004·Molecular and Cellular Biology·Pablo Rodriguez-VicianaFrank McCormick
Oct 11, 2012·Journal of Signal Transduction·Janice Wai Sze Law, Alan Yiu Wah Lee
Feb 20, 2010·BMC Cell Biology·Matthew W ConklinPatricia J Keely
Aug 25, 2012·World Journal of Gastroenterology : WJG·Raghibul HasanRanju Ralhan
Jun 15, 2000·Proceedings of the National Academy of Sciences of the United States of America·T AkagiH Hanafusa
Dec 30, 2014·Expert Opinion on Drug Delivery·Ana Tari Ashizawa, Jorge Cortes
May 16, 2009·EMBO Reports·Yasuhiro SaitoManabu Negishi
Dec 6, 2005·Experimental Cell Research·Guido SeriniFederico Bussolino

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