Rapamycin dissociates p70(S6K) activation from DNA synthesis stimulated by bombesin and insulin in Swiss 3T3 cells.

The Journal of Biological Chemistry
D J WithersEnrique Rozengurt

Abstract

Phosphorylation and subsequent activation of p70 S6 kinase (S6K) are events that are highly conserved in the cellular response to mitogens. The neuropeptide bombesin, which is a potent mitogen for Swiss 3T3 cells, stimulated a time- and dose-dependent activation of p70(S6K) as determined by gel mobility shift and immune complex kinase assays. This effect was inhibited by the immunosuppressant rapamycin at 10 nM, which also completely abolished bombesin-stimulated DNA synthesis at identical concentrations. In striking contrast, the combination of bombesin and insulin in synergy stimulated maximum DNA synthesis in these cells despite persistent inhibition of p70(S6K) by rapamycin throughout G1. These results indicate that activation of p70(S6K) is not required for the transition of quiescent cells to the S phase of the cell cycle. The inhibitory effects of rapamycin on bombesin-stimulated cell cycle progression did not involve accumulation of the cyclin-dependent kinase inhibitor p27(kip1) but a striking inhibition of the expression of cyclin D1. This effect was circumvented by bombesin with insulin, suggesting that a rapamycin-insensitive pathway stimulated by this combination leads to cyclin D1 expression. Thus, these findings,...Continue Reading

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Citations

May 19, 2004·Biochemical and Biophysical Research Communications·Chintda SantiskulvongEnrique Rozengurt
Sep 6, 2007·Journal of Cellular Physiology·Enrique Rozengurt
Sep 10, 1999·The Journal of Biological Chemistry·F ViñalsJ Pouysségur
Sep 28, 2001·The Journal of Biological Chemistry·J M BoylanP A Gruppuso
Feb 19, 2004·The Journal of Biological Chemistry·Susan W Y ChengPeter R Shepherd
Mar 14, 2001·American Journal of Physiology. Cell Physiology·T Chiu, E Rozengurt
Aug 15, 2001·American Journal of Physiology. Cell Physiology·C SantiskulvongE Rozengurt
Jul 25, 2020·Scientific Reports·Sam R J HoareLloyd J Bridge
Jul 26, 2005·Critical Reviews in Oncology/hematology·Brian K Law

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