RAPT1, A MAMMALIAN HOMOLOG OF YEAST TOR, INTERACTS WITH THE FKBP12 RAPAMYCIN COMPLEX

Rapamycin is a potent immunosuppressant that blocks the G(1)/S transit ion 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 iso lated mammalian clones that interact with the human FK506/rapamycin-bi nding protein (FKBP12) in the presence of rapamycin. Specific interact ors, designated RAPT1, encode overlapping sequences homologous to yeas t Tor, a putative novel phosphatidylinositol 3-kinase. A region of 133 amino acids of RAPT1 is sufficient for binding to the FKBP12/rapamyci n complex. The corresponding region in yeast Tor contains the serine r esidue that when mutated to arginine confers resistance to rapamycin. Introduction of this mutation into RAPT1 abolishes its interaction wit h the FKBP12/rapamycin complex.