Novel regulatory mechanisms of mTOR signaling.

As a master regulator of cellular processes ranging from cell growth and proliferation to differentiation, the mammalian target of rapamycin (mTOR) is critically involved in a complex signaling network. mTOR appears to govern an amino acid sensing pathway that integrates with a phosphatidylinositol 3-kinase-dependent mitogenic pathway to activate the downstream effectors. Recent findings have revealed some unexpected regulatory mechanisms of mTOR signaling. A direct link between mTOR and mitogenic signals is found to be mediated by the lipid second messenger phosphatidic acid. In addition, cytoplasmic-nuclear shuttling of mTOR appears to be required for the cytoplasmic functions of this protein. A new picture of the rapamycin-sensitive signaling network is emerging, with implications in putative upstream regulators and additional downstream targets for mTOR.