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Genes Cells. 2000 Sep;5(9):765-75.

Carboxyl-terminal region conserved among phosphoinositide-kinase-related kinases is indispensable for mTOR function in vivo and in vitro.

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Biosignal Research Center, Kobe University, Kobe 657-8501, Japan.

Erratum in

  • Genes Cells 2000 Nov;5(11):949-52.



The mammalian target of rapamycin (mTOR) belongs to the family of phosphoinositide (PI)-kinase-related kinases that includes the ataxia-telangiectasia gene product (ATM). mTOR plays a critical role in controlling translational effectors such as p70 S6 kinase alpha (p70 alpha) and eukaryotic initiation factor 4E binding protein 1 (4EBP1).


We show that the C-terminal region of mTOR, which is highly conserved among the PI-kinase-related kinases, plays a critical role in the mTOR protein kinase activity. Deletion of the C-terminal residues did not adversely affect the expression of mTOR, but caused a nearly complete loss of the mTOR protein kinase activity toward both 4EBP1 and p70 alpha in vitro. These deletions also abolished the ability of a rapamycin-resistant mTOR mutant to rescue the activity of p70 alpha from inhibition induced by rapamycin in vivo. Furthermore, replacement of Trp2545, a conserved residue in the C-terminal region throughout the PI-kinase-related kinase family, abolished the function of the mTOR kinase, both in vivo and in vitro. However, substitution of 32 C-terminal residues of mTOR with those of ATM did not restore the mTOR function.


These findings define an indispensable role for the noncatalytic C-terminal region of mTOR and indicate that, although this highly conserved region may be important throughout the PI-kinase-related kinase family, it is not functionally interchangeable within the family.

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