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.
Pubmed ID: 11493700 RIS Download
Animals | Apoptosis | Carrier Proteins | Cell Division | Cell Line | Cell Survival | Enzyme Inhibitors | Insulin-Like Growth Factor I | Interleukin-3 | Mitochondria | Models, Biological | Phosphorylation | Point Mutation | Protein Processing, Post-Translational | Rats | Recombinant Fusion Proteins | Ribosomal Protein S6 Kinases | Sirolimus | bcl-Associated Death Protein