mTOR is the rapamycin-sensitive kinase that confers mechanically-induced phosphorylation of the hydrophobic motif site Thr(389) in p70(S6k).

Mechanical stretch induces phosphorylation of the hydrophobic motif site Thr(389) in p70(S6k) through a rapamycin-sensitive (RS) pathway that involves a unique PI3K-independent mechanism. Rapamycin is considered to be a highly specific inhibitor of the protein kinase mTOR; however, mTOR is also considered to be a PI3K-dependent signaling molecule. Thus, questions remain as to whether mTOR is the RS element that confers mechanically-induced signaling to p70(S6k)(389). In this study, rapamycin-resistant mutants of mTOR along with mechanical stretch were used to address this question. The results indicate that mTOR is the RS element and reveal that mTOR signaling can be activated through a PI3K-independent mechanism.