p70S6 kinase signals cell survival as well as growth, inactivating the pro-apoptotic molecule BAD
Copyright policy )p70S6 kinase signals cell survival as well as growth, inactivating the pro-apoptotic molecule BAD
Cytokines often deliver simultaneous, yet distinct, cell growth and cell survival signals. The 70-kDa ribosomal protein S6 kinase (p70S6K) is known to regulate cell growth by inducing protein synthesis components. We purified membrane-based p70S6K as a kinase responsible for site-specific phosphorylation of BAD, which inactivates this proapoptotic molecule. Rapamycin inhibited mitochondrial-based p70S6K, which prevented phosphorylation of Ser-136 on BAD and blocked cell survival induced by insulin-like growth factor 1 (IGF-1). Moreover, IGF-1-induced phosphorylation of BAD Ser-136 was abolished in p70S6K-deficient cells. Thus, p70S6K is itself a dual pathway kinase, signaling cell survival as well as growth through differential substrates which include mitochondrial BAD and the ribosomal subunit S6, respectively.
- Harvard University United States
- University of Southern Denmark Denmark
- Howard Hughes Medical Institute United States
- Dana-Farber Cancer Institute United States
- University of Florida United States
Cell Survival, Recombinant Fusion Proteins, Apoptosis, Models, Biological, Cell Line, Models, Animals, Point Mutation, Enzyme Inhibitors, Insulin-Like Growth Factor I, Phosphorylation, Protein Processing, Sirolimus, Ribosomal Protein S6 Kinases, Post-Translational, Biological, Mitochondria, Rats, Interleukin-3, bcl-Associated Death Protein, Carrier Proteins, Protein Processing, Post-Translational, Cell Division
Cell Survival, Recombinant Fusion Proteins, Apoptosis, Models, Biological, Cell Line, Models, Animals, Point Mutation, Enzyme Inhibitors, Insulin-Like Growth Factor I, Phosphorylation, Protein Processing, Sirolimus, Ribosomal Protein S6 Kinases, Post-Translational, Biological, Mitochondria, Rats, Interleukin-3, bcl-Associated Death Protein, Carrier Proteins, Protein Processing, Post-Translational, Cell Division
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