The mammalian target of rapamycin, commonly known as mTOR, is a serine/threoninekinase that regulates translation and cell division. Nutrient availability influences mTOR so that when cells are not able to grow to normal size they will not undergo cell division. Current research indicates that mTOR integrates input from multiple upstream pathways, including insulin, growth factors, nutrients, mitogens and energy.
Rapamycin is a fungal derivation that halts protein synthesis. mTOR is activated by insulin or leucine, which cause phosphorylation of proteins that regulate transcription. If the mTOR pathway is not activated by insulin or leucine, proteins in the body will eventually undergo degradation.
mTOR pathway is inhibited by rapamycin an immunosupressive drug. Action of rapamycin is thought to occurs downstream of mTOR : mTOR inhibition of phosphatase PP2A is derepressed by rapamycin, possibly by way of another phosphatase, PP5[#endnote_Huang2004].
mTOR has recently been suggested to play a part in the regulation of two pathways, referred to as TORC1 and TORC2 (for TOR Complex 1 and 2). TORC1 is a protein complex consisting of at least mTOR, LST8 and the protein raptor which, when activated by upstream kinases such as PDK1 and Akt, can phosphorylate its known substrates p70S6 Kinase and 4EBP1 to regulate protein translation and ultimately cell size.
TORC2 is a complex consisting of at lease mTOR and rictor. The function of TORC2 is as yet unknown. Only the TORC1 complex is sensitive to rapamycin.
References
↑ Shile Huang, Lili Shu, John Easton, Franklin C. Harwood, Glen S. Germain, Hidenori Ichijo and Peter J. Houghton "Inhibition of Mammalian Target of Rapamycin Activates Apoptosis Signal-regulating Kinase 1 Signaling by Suppressing Protein Phosphatase 5 Activity" in Journal of Biological Chemistry (2004) Volume 279, pages 36490-36496. Entrez PubMed [15218033]
