p70S6 kinase signals cell survival as well as growth, inactivating the pro-apoptotic molecule BAD.
Journal:
Proc. Natl. Acad. Sci. U.S.A. 2001 AugAuthors:
Harada H, Andersen JS, Mann M, Terada N, Korsmeyer SJ
Abstract
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 insul
...[more]in-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.[less]
Mesh Headings:
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