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| Subject Categories: Signal Transduction |
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| The EMBO Journal
(2006) 25, 3546–3555, doi:10.1038/sj.emboj.7601239 Published online 27 July 2006 |
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| Rapamycin activates Tap42-associated phosphatases by abrogating their association with Tor complex 1 |
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| Gonghong Yan, Xiaoyun Shen and Yu Jiang |
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Department of Pharmacology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA To whom correspondence should be addressed Yu Jiang, Department of Pharmacology, University of Pittsburgh School of Medicine, E1357 Biomedical Science Tower, 200 Lothrop Street, Pittsburgh, PA 15213, USA. Tel.: +1 412 648 3390; Fax: +1 412 648 1945; E-mail: jiang@server.pharm.pitt.edu Received 7 September 2005; Accepted 26 June 2006; Published online 27 July 2006. |
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| Abstract |
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| 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. |
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| Keywords: PP2A, rapamycin, Sit4, Tap42, Tor kinases |
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