RAPT1, a mammalian homolog of yeast Tor, interacts with the FKBP12/rapamycin complex.
Rapamycin is a potent immunosuppressant that blocks the G1/S transition in antigen-activated T cells and in yeast. The similar effects of rapamycin in animal cells and yeast suggest that the biochemical steps affected by rapamycin are conserved. Using a two-hybrid system we isolated mammalian clones that interact with the human FK506/rapamycin-binding protein (FKBP12) in the presence of rapamycin. Specific interactors, designated RAPT1, encode overlapping sequences homologous to yeast Tor, a putative novel phosphatidylinositol 3-kinase. A region of 133 amino acids of RAPT1 is sufficient for binding to the FKBP12/rapamycin complex. The corresponding region in yeast Tor contains the serine residue that when mutated to arginine confers resistance to rapamycin. Introduction of this mutation into RAPT1 abolishes its interaction with the FKBP12/rapamycin complex.
Chiu
M I
MI
Mitotix, Inc., Cambridge, MA 02139.
Katz
H
H
Berlin
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D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000378:metabolism*; D003001:Cloning, Molecular; D017931:DNA Primers / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000378:metabolism*; D015870:Gene Expression; D006360:Heat-Shock Proteins / Q000378:metabolism*; D046911:Macromolecular Substances; D051379:Mice; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics / Q000378:metabolism*; D011090:Polyenes / Q000378:metabolism*; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D020123:Sirolimus; D013329:Structure-Activity Relationship; D058570:TOR Serine-Threonine Kinases; D022021:Tacrolimus Binding Proteins; D014018:Tissue Distribution
D002352:Carrier Proteins; D017931:DNA Primers; D004268:DNA-Binding Proteins; D006360:Heat-Shock Proteins; D046911:Macromolecular Substances; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D011090:Polyenes; D012333:RNA, Messenger; D020123:Sirolimus; D058570:TOR Serine-Threonine Kinases; D022021:Tacrolimus Binding Proteins; C546842:MTOR protein, human; C546843:mTOR protein, mouse