The molecular interplay between the phosphoinositide 3-kinase (PI3K) pathway and mammalian target of rapamycin (mTOR) signalling in the control of cell growth and proliferation has been the subject of much interest and debate amongst cell biologists. A recent escalation of research in this area has come from the discovery of the tuberous sclerosis complex gene products, tuberin and hamartin, as central regulators of mTOR activation. The PI3K effector Akt/protein kinase B has been found to directly phosphorylate tuberin and is thereby thought to activate mTOR through inhibition of the tuberin–hamartin complex. The many recent studies aimed at defining the molecular nature of this revamped PI3K/Akt/mTOR pathway are reviewed here. The collective data discussed have laid the groundwork for important new insights into the many cancers caused by aberrant PI3K activation and the clinically challenging tuberous sclerosis complex disease and have suggested a possible means of treatment for both.

Abbreviations used: PI3K, phosphoinositide 3-kinase; mTOR, mammalian target of rapamycin; TSC, tuberous sclerosis complex; S6K1, 70 kDa ribosomal S6 kinase; d, Drosophila; GAP, GTPase-activating protein; 4E-BP1, eukaryotic initiation factor 4E-binding protein 1; siRNA, small interfering RNA.

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Author notes

TSC Genes – Novel Players in the Growth Regulation Network, a Biochemical Society Focused Meeting held at The Royal Society of Medicine, London, 3 February 2003