Rheb binding to mTOR is regulated by amino acid sufficiency.

@article{citeulike:191273, abstract = {The removal of extracellular amino acids, or leucine alone inhibits the ability of mTOR to signal to the raptor-dependent substrates, p70 S6 kinase and 4E-BP. This inhibition can be overcome by overexpression of the Rheb GTPase. Rheb binds directly to the aminoterminal lobe of the mTOR catalytic domain, and activates mTOR kinase in a GTP dependent manner. Herein we show that the binding of Rheb to endogenous and recombinant mTOR is reversibly inhibited by withdrawal of all extracellular amino acids or just leucine. The effect of amino acid withdrawal is not attributable to changes in Rheb-GTP charging; amino acid withdrawal does not alter the GTP charging of recombinant Rheb. Moreover, the binding of mTOR to Rheb mutants that are unable to bind guanyl nucleotide in vivo is also inhibited by amino withdrawal. The inhibitory effect of amino acid withdrawal is exerted through an action on mTOR, at a site largely distinct from that responsible for the binding of Rheb; deletion of the larger, carboxyterminal lobe of the mTOR catalytic domain eliminates the inhibitory effect of amino acid withdrawal on Rheb binding, without altering Rheb binding per se. The lesser ability of the mTOR catalytic domain to bind Rheb after amino acid withdrawal does not persist after extraction and purification of the mTOR polypeptide. Amino acid withdrawl may generate an inhibitor of the Rheb-mTOR interaction that interferes with the signaling function of TOR complex 1.}, address = {Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114.}, author = {Long, Xiaomeng and Ortiz-Vega, Sara and Lin, Yenshou and Avruch, Joseph }, citeulike-article-id = {191273}, doi = {http://dx.doi.org/10.1074/jbc.C500169200}, issn = {0021-9258}, journal = {J Biol Chem}, keywords = {mtor, nutrients, rheb}, month = {May}, posted-at = {2005-05-12 11:09:01}, priority = {2}, title = {Rheb binding to mTOR is regulated by amino acid sufficiency.}, url = {http://dx.doi.org/10.1074/jbc.C500169200}, year = {2005} }

TY - JOUR ID - citeulike:191273 L3 - citeulike-article-id:191273 TI - Rheb binding to mTOR is regulated by amino acid sufficiency. JF - J Biol Chem AD - Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114. SN - 0021-9258 N2 - The removal of extracellular amino acids, or leucine alone inhibits the ability of mTOR to signal to the raptor-dependent substrates, p70 S6 kinase and 4E-BP. This inhibition can be overcome by overexpression of the Rheb GTPase. Rheb binds directly to the aminoterminal lobe of the mTOR catalytic domain, and activates mTOR kinase in a GTP dependent manner. Herein we show that the binding of Rheb to endogenous and recombinant mTOR is reversibly inhibited by withdrawal of all extracellular amino acids or just leucine. The effect of amino acid withdrawal is not attributable to changes in Rheb-GTP charging; amino acid withdrawal does not alter the GTP charging of recombinant Rheb. Moreover, the binding of mTOR to Rheb mutants that are unable to bind guanyl nucleotide in vivo is also inhibited by amino withdrawal. The inhibitory effect of amino acid withdrawal is exerted through an action on mTOR, at a site largely distinct from that responsible for the binding of Rheb; deletion of the larger, carboxyterminal lobe of the mTOR catalytic domain eliminates the inhibitory effect of amino acid withdrawal on Rheb binding, without altering Rheb binding per se. The lesser ability of the mTOR catalytic domain to bind Rheb after amino acid withdrawal does not persist after extraction and purification of the mTOR polypeptide. Amino acid withdrawl may generate an inhibitor of the Rheb-mTOR interaction that interferes with the signaling function of TOR complex 1. KW - mtor KW - nutrients KW - rheb AU - Long, Xiaomeng AU - Ortiz-Vega, Sara AU - Lin, Yenshou AU - Avruch, Joseph PY - 2005/05/05/ UR - http://dx.doi.org/10.1074/jbc.C500169200 ER -