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

Yan, Gonghong; Shen, Xıaoyun; Jiang, Yu

doi:10.1038/sj.emboj.7601239

Cited by 105 publications

(132 citation statements)

References 31 publications

(77 reference statements)

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“…In actively growing cells, the Tap42-associated phosphatase complexes reside mainly at membranes where they associate with TORC1. Rapamycin treatment or nitrogen starvation abrogates the TORC1 association and releases the Tap42-associated phosphatase complex into the cytosol (Yan et al 2006). Once cytoplasmic, this complex then slowly dissociates, presumably concomitant with the dephosphorylation of Tap42 (Zheng and Jiang 2005;Yan et al 2006).…”

Section: Rapamycin-sensitive Signalling Via Torc1mentioning

confidence: 99%

“…Rapamycin treatment or nitrogen starvation abrogates the TORC1 association and releases the Tap42-associated phosphatase complex into the cytosol (Yan et al 2006). Once cytoplasmic, this complex then slowly dissociates, presumably concomitant with the dephosphorylation of Tap42 (Zheng and Jiang 2005;Yan et al 2006). Several studies revealed an important role for yet another player in TORC1-dependent regulation of PP2Ac and Sit4, i.e.…”

Section: Rapamycin-sensitive Signalling Via Torc1mentioning

confidence: 99%

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Life in the midst of scarcity: adaptations to nutrient availability in Saccharomyces cerevisiae

et al. 2010

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Cells of all living organisms contain complex signal transduction networks to ensure that a wide range of physiological properties are properly adapted to the environmental conditions. The fundamental concepts and individual building blocks of these signalling networks are generally well-conserved from yeast to man; yet, the central role that growth factors and hormones play in the regulation of signalling cascades in higher eukaryotes is executed by nutrients in yeast. Several nutrient-controlled pathways, which regulate cell growth and proliferation, metabolism and stress resistance, have been defined in yeast. These pathways are integrated into a signalling network, which ensures that yeast cells enter a quiescent, resting phase (G 0 ) to survive periods of nutrient scarceness and that they rapidly resume growth and cell proliferation when nutrient conditions become favourable again. A series of well-conserved nutrient-sensory protein kinases perform key roles in this signalling network: i.e. Snf1, PKA, Tor1 and Tor2, Sch9 and Pho85-Pho80. In this review, we provide a comprehensive overview on the current understanding of the signalling processes mediated via these kinases with a particular focus on how these individual pathways converge to signalling networks that ultimately ensure the dynamic translation of extracellular nutrient signals into appropriate physiological responses.

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Section: Rapamycin-sensitive Signalling Via Torc1mentioning

confidence: 99%

Section: Rapamycin-sensitive Signalling Via Torc1mentioning

confidence: 99%

Life in the midst of scarcity: adaptations to nutrient availability in Saccharomyces cerevisiae

et al. 2010

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“…The phosphatase 2A associated protein of 42-kDa (Tap42) associates with the catalytic subunits of the yeast PP2A subfamily (PP2A, PP4, and PP6). Tap42 is a major effector of TOR signaling in yeast that interacts with the PP2A subfamily following phosphorylation by TOR [11]. Mammalian cells express a protein (α4/mTap42) that has 23% amino acid sequence identity with yeast Tap42.…”

Section: Introductionmentioning

confidence: 99%

Functional analysis of the PP2A subfamily of protein phosphatases in regulating Drosophila S6 kinase

Bielinski¹,

Mumby²

2007

Experimental Cell Research

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Phosphorylation and activation of ribosomal S6 protein kinase is an important link in the regulation of cell size by the target of rapamycin (TOR) protein kinase. A combination of selective inhibition and RNA interference were used to test the roles of members of the PP2A subfamily of protein phosphatases in dephosphorylation of Drosophila S6 kinase (dS6K). Treatment of Drosophila Schneider 2 cells with calyculin A, a selective inhibitor of PP2A-like phosphatases, resulted in a 7-fold increase in the basal level of dS6K phosphorylation at the TOR phosphorylation site (Thr398) and blocked dephosphorylation following inactivation of TOR by amino acid starvation or rapamycin treatment. Knockdown of the PP2A catalytic subunit increased basal dS6K phosphorylation and inhibited dephosphorylation induced by amino acid withdrawal. In contrast, depletion of the catalytic subunits of the other two members of the subfamily did not enhance dS6K phosphorylation. Knockdown of PP4 caused a 20% decrease in dS6K phosphorylation and knockdown of PP6 had no effect. Knockdown of the Drosophila B56-2 subunit resulted in enhanced dephosphorylation of dS6K following removal of amino acids. In contrast, knockdown of the homologs of the other PP2A regulatory subunits had no effects. Knockdown of the Drosophila homolog of the PP2A/PP4/PP6 interaction protein α4/Tap42 did not affect S6K phosphorylation, but did induce apoptosis. These results indicate that PP2A, but not other members of this subfamily, is likely to be a major S6K phosphatase in intact cells and is consistent with an important role for this phosphatase in the TOR pathway.

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“…A prominent role for endogenous membranes of the protein secretory pathway as a platform for Tor signaling has begun to emerge: (i) different components of the Tor protein complexes, termed TORC1 and TORC2, as well as the Tap42-Sit4 phosphatase complex, have been localized to endosomal and vacuolar compartments (5)(6)(7)(8)(9)(10)(11)(12); (ii) a function for the Golgi Ca 2ϩ /Mn 2ϩ ATPase Pmr1 in negatively regulating TORC1 signaling has been demonstrated (13); and (iii) recent studies have shown genetic interactions between TORC1 and different components of the protein-sorting machinery, including those of the class C Vps complex that functions in docking and fusion of vesicles with the Golgi, endosomes, and vacuoles (refs. 9, 14, and reviewed in ref.…”

mentioning

confidence: 99%

Nuclear translocation of Gln3 in response to nutrient signals requires Golgi-to-endosome trafficking in Saccharomyces cerevisiae

Puria

Zurita-Martinez

Cárdenas

2008

Proc. Natl. Acad. Sci. U.S.A.

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The yeast Saccharomyces cerevisiae has developed specialized mechanisms that enable growth on suboptimal nitrogen sources. Exposure of yeast cells to poor nitrogen sources or treatment with the Tor kinase inhibitor rapamycin elicits activation of Gln3 and transcription of nitrogen catabolite-repressed (NCR) genes whose products function in scavenging and metabolizing nitrogen. Here, we show that mutations in class C and D Vps components, which mediate Golgi-to-endosome vesicle transport, impair nuclear translocation of Gln3, NCR gene activation, and growth in poor nitrogen sources. In nutrient-replete conditions, a significant fraction of Gln3 is peripherally associated with light membranes and partially colocalizes with Vps10-containing foci. These results reveal a role for Golgi-to-endosome vesicular trafficking in TORC1-controlled nuclear translocation of Gln3 and support a model in which Tor-mediated signaling in response to nutrient cues occurs in these compartments. These findings have important implications for nutrient sensing and growth control via mTor pathways in metazoans.rapamycin action ͉ Tor signaling

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

Cited by 105 publications

References 31 publications

Life in the midst of scarcity: adaptations to nutrient availability in Saccharomyces cerevisiae

Life in the midst of scarcity: adaptations to nutrient availability in Saccharomyces cerevisiae

Functional analysis of the PP2A subfamily of protein phosphatases in regulating Drosophila S6 kinase

Nuclear translocation of Gln3 in response to nutrient signals requires Golgi-to-endosome trafficking in Saccharomyces cerevisiae

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