TOR KINASE DOMAINS ARE REQUIRED FOR 2 DISTINCT FUNCTIONS, ONLY ONE OFWHICH IS INHIBITED BY RAPAMYCIN

The rapamycin-sensitive signaling pathway is required to transduce spe cific mitogenic signals to the cell cycle machinery responsible for G1 progression. Genetic studies in yeast identified two related genes on this pathway, TOR1 and TOR2, thought to encode novel phosphatidylinos itol kinases. We now show that an intact kinase domain is required for the G1 cell cycle functions of both proteins, for the ability of a mu tation in a neighboring FKBP12-rapamycin-binding domain of the TOR1 pr otein to inhibit the growth of yeast cells when overexpressed, and for the essential function of the TOR2 protein. The G1 function of both T OR proteins is sensitive to rapamycin, but the essential function of T OR2 is not. Thus, FKBP12-rapamycin does not appear to inhibit the kina se activity of TOR proteins in a general way; instead, it may interfer e selectively with TOR protein binding to or phosphorylation of G1 eff ecters.