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Reference - PMID:22976295 - Psk1, an AGC kinase family member in fission yeast, is directly phosphorylated and controlled by TORC1 and functions as S6 kinase.

Reference summary

PubMed ID
PMID:22976295
Title
Psk1, an AGC kinase family member in fission yeast, is directly phosphorylated and controlled by TORC1 and functions as S6 kinase.
Authors
Nakashima A, Otsubo Y, Yamashita A, Sato T, Yamamoto M, Tamanoi F
Citation
J Cell Sci 2012 Dec 01;125(Pt 23):5840-9
Publication year
2012
Abstract
Target of rapamycin (TOR), an evolutionarily conserved serine/threonine protein kinase, plays pivotal roles in several important cellular processes in eukaryotes. In the fission yeast Schizosaccharomyces pombe, TOR complex 1 (TORC1), which includes Tor2 as a catalytic subunit, manages the switch between cell proliferation and differentiation by sensing nutrient availability. However, little is known about the direct target of TORC1 that plays key roles in nutrient-dependent TORC1 signaling in fission yeast. Here we report that in fission yeast, three AGC kinase family members, named Psk1, Sck1 and Sck2, which exhibit high homology with human S6K1, are phosphorylated under nutrient-rich conditions and are dephosphorylated by starvation conditions. Among these, Psk1 is necessary for phosphorylation of ribosomal protein S6. Furthermore, Psk1 phosphorylation is regulated by TORC1 in nutrient-dependent and rapamycin-sensitive manners in vivo. Three conserved regulatory motifs (the activation loop, the hydrophobic and the turn motifs) in Psk1 are phosphorylated and these modifications are required for Psk1 activity. In particular, phosphorylation of the hydrophobic motif is catalyzed by TORC1 in vivo and in vitro. Ksg1, a homolog of PDK1, is also important for Psk1 phosphorylation in the activation loop and for its activity. The TORC1 components Pop3, Toc1 and Tco89, are dispensable for Psk1 regulation, but disruption of pop3(+) causes an increase in the sensitivity of TORC1 to rapamycin. Taken together, these results provide convincing evidence that TORC1/Psk1/Rps6 constitutes a nutrient-dependent signaling pathway in fission yeast.

Annotation

GO biological process

GO:1904262 - negative regulation of TORC1 signaling

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GO:2000767 - positive regulation of cytoplasmic translation

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GO:0038202 - TORC1 signaling

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GO molecular function

GO:0004674 - protein serine/threonine kinase activity

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GO:0004711 - ribosomal protein S6 kinase activity

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Modification

MOD:00046 - O-phospho-L-serine

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MOD:00047 - O-phospho-L-threonine

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MOD:00696 - phosphorylated residue

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Multi-locus phenotype

FYPO:0002033 - abolished protein phosphorylation during vegetative growth

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FYPO:0001407 - decreased cell population growth on glucose carbon source

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FYPO:0001838 - decreased protein phosphorylation during vegetative growth

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FYPO:0001029 - resistance to canavanine

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Single locus phenotype

FYPO:0001384 - abolished protein kinase activity

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FYPO:0002033 - abolished protein phosphorylation during vegetative growth

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FYPO:0001407 - decreased cell population growth on glucose carbon source

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FYPO:0001324 - decreased protein level during vegetative growth

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FYPO:0001838 - decreased protein phosphorylation during vegetative growth

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FYPO:0002700 - increased protein kinase activity

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FYPO:0004949 - increased protein phosphorylation during cellular response to rapamycin

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FYPO:0002681 - increased protein phosphorylation during nitrogen starvation

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FYPO:0004422 - normal protein phosphorylation

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FYPO:0000776 - normal protein phosphorylation during vegetative growth

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FYPO:0001029 - resistance to canavanine

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FYPO:0002060 - viable vegetative cell population

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