P70S6 kinase

p70S6 kinase or p70S6K is a serine/threonine kinase that acts downstream of PIP3 and phosphoinositide-dependent kinase-1 in the PI3 kinase pathway.^[1] As the name suggests, its target substrate is the S6 ribosomal protein.^[2] Phosphorylation of S6 induces protein synthesis at the ribosome.

mTOR

P70S6 kinase is in a signaling pathway that includes mTOR (the mammalian target of rapamycin). mTOR can be activated in distinct ways, thereby activating p70S6K. For example, branched chain amino acids such as leucine are sufficient to activate mTOR, resulting in an increase in p70S6K phosphorylation (and thereby activating it). mTOR is also in a pathway downstream of the kinase Akt. Akt is typically activated upon stimulation of a cell with a growth factor (such as IGF-1). Akt then activates mTOR (by inhibiting the Tsc complex), leading to p70S6K activation.

Physical exercise activates protein synthesis via phosphorylation (activation) of p70S6K in a pathway that is dependent on mTOR. This has been demonstrated by using an inhibitor of mTOR, rapamycin, to block an increase in muscle mass, despite increases in load (e.g., exercise). Exercise has been shown to increase levels of IGF-1 in muscle, thus inducing the IGF-1/PI3K/Akt/P70S6K signaling pathway, and thereby increasing the protein synthesis required to build muscle.

References

1. ^ Chung J, Grammer TC, Lemon KP, Kazlauskas A, Blenis J. (1994). "PDGF- and insulin-dependent pp70S6k activation mediated by phosphatidylinositol-3-OH kinase". Nature 370 (6484): 71–75. doi:10.1038/370071a0. PMID 8015612. 
2. ^ Chung J, Kuo CJ, Crabtree GR, Blenis J. (1992). "Rapamycin-FKBP specifically blocks growth-dependent activation of and signaling by the 70 kd S6 protein kinases.". Cell 69 (7): 1227–1236. doi:10.1016/0092-8674(92)90643-Q. PMID 1377606.