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The mammalian target of rapamycin (mTOR) is a master integrator of cell energy state, nutrient status, and growth factor stimulation. This kinase is part of two distinct complexes, mTORC1 and mTORC2, and the network that regulates these two complexes is interconnected with distinct and overlapping inputs and outputs. Research published in Science Signaling has revealed new connections between epidermal growth factor receptors and the mTOR pathway, and new insight into the roles of mTOR signaling in vascular disease. The Perspectives in this issue highlight how new pharmacological tools and the ability to knock down the function of complex-specific subunits are providing new insight into the regulation and functions of these complexes in physiological contexts, as well as providing new avenues for therapeutic intervention in diseases associated with aberrant activity of these complexes.
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