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 su rvival 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 phosphoryl ation of BAD, which inactivates this proapoptotic molecule. Rapamycin inhib ited 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 abolishe d in p70S6K-deficient cells. Thus, p70S6K is itself a dual pathway kinase, signaling cell survival as well as growth through differential substrates w hich include mitochondrial BAD and the ribosomal subunit S6, respectively.