Rapamycin activates Tap42-associated phosphatases by abrogating their association with Tor complex 1.

In Saccharomyces cerevisiae, the Tap42-phosphatase complexes are major targets of the Tor kinases in the rapamycin-sensitive signaling pathway. The immunosuppressive agent, rapamycin, induces a prompt activation of the Tap42-associated phosphatases, which is vitally important in Tor-mediated transcriptional regulation. However, the mechanism for the rapid phosphatase activation is poorly understood. In ...
this study, we show that the Tap42-phosphatase complexes exist mainly on membrane structures through their association with Tor complex 1 (TORC1). Rapamycin abrogates this association and releases the Tap42-phosphatase complexes into the cytosol. Disassembly of the Tap42-phosphatase complexes occurs subsequently, following the release but at a much slower rate, presumably caused by Tap42 dephosphorylation. Release of the Tap42-phosphatase complexes from membrane structures also occurs when cells are deprived of nutrient. These findings suggest that the association of the Tap42-phosphatase complexes with TORC1 represents an important mechanism by which nutrient controls Tor signaling activity. In addition, our data support a model in which rapamycin acts not by inhibiting the kinase activity of Tor but by disrupting its interaction with downstream targets.
Mesh Terms:
1-Phosphatidylinositol 3-Kinase, Adaptor Proteins, Signal Transducing, Cell Membrane, Cytosol, Enzyme Activation, Immunoprecipitation, Models, Biological, Phosphoric Monoester Hydrolases, Phosphotransferases (Alcohol Group Acceptor), Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Signal Transduction, Sirolimus
EMBO J.
Date: Aug. 09, 2006
Download Curated Data For This Publication
70895
Switch View:
  • Interactions 7