BACKGROUND p70S6k is a Ser/Thr kinase that is stimulated by a variety of mitogens, such as insulin, 12-O-tetradecanoylphorbol-13-acetate, and growth factors. The activation of p70S6k is attributable to phosphorylation of Ser/Thr residues on multiple sites, such as Thr389, Ser424, and Thr421. Upon activation, p70S6k phosphorylates the S6 protein of the 40S ribosomal subunit. Phosphorylated S6 directs the translational machinery toward increasing the production of translational machinery components, such as ribosomal proteins and elongation factors. Thus, p70S6k plays an important role in cell growth, transformation, and transition of cell cycle in mammalian cells.1
It is believed that PI-3 kinase and its downstream effector, the protein kinase Akt, act as signaling intermediates that link cell surface receptors to p70S6k, typically activated upon stimulation of a cell with a growth factor (such as IGF-1).2 It has also been reported that the PI-3 kinase structurally related enzyme, mTOR (also termed FRAP or RAFT), is also involved in the regulation of phosphorylation of p70S6k. Branched chain amino acids, such as leucine, are also sufficient for the activation of mTOR, resulting in an increase in p70S6K phosphorylation.3 On the other hand, AMPK plays important role in negatively regulating mTOR/p70 S6 kinase pathway.4
REFERENCES
1. Pearson RB & Thomas G: Prog. Cell Cycle Res. 1:21-32, 1995.
2. Chung J et al.: Nature 370:71-75, 1994.
3. Ban H et al.: Int J Mol Med. 13:537-43, 2004.
4. Chan AYM & Dyck JRB: Can. J. Physiol. Pharmacol. 83:24–28, 2005.
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