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TORC1-regulated protein kinase Npr1 phosphorylates Orm to stimulate complex sphingolipid synthesis

Shimobayashi, Mitsugu and Oppliger, Wolfgang and Moes, Suzette and Jenö, Paul and Hall, Michael N.. (2013) TORC1-regulated protein kinase Npr1 phosphorylates Orm to stimulate complex sphingolipid synthesis. Molecular Biology of the Cell, 24 (6). pp. 870-881.

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Official URL: http://edoc.unibas.ch/dok/A6070824

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Abstract

The evolutionarily conserved Orm1 and Orm2 proteins mediate sphingolipid homeostasis. However, the homologous Orm proteins and the signaling pathways modulating their phosphorylation and function are incompletely characterized. Here we demonstrate that inhibition of nutrient-sensitive target of rapamycin complex 1 (TORC1) stimulates Orm phosphorylation and synthesis of complex sphingolipids in Saccharomyces cerevisiae. TORC1 inhibition activates the kinase Npr1 which directly phosphorylates and activates the Orm proteins. Npr1-phosphorylated Orm1 and Orm2 stimulate de novo synthesis of complex sphingolipids downstream of serine palmitoyltransferase (SPT). Complex sphingolipids in turn stimulate plasma membrane localization and activity of the nutrient scavenging general amino acid permease Gap1. Thus, activation of Orm and complex sphingolipid synthesis upon TORC1 inhibition is a physiological response to starvation.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Growth & Development > Biochemistry (Hall)
UniBasel Contributors:Hall, Michael N. and Shimobayashi, Mitsugu and Oppliger, Wolfgang and Moes, Suzette and Jenö, Paul
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:American Society for Cell Biology
ISSN:1059-1524
e-ISSN:1939-4586
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
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Last Modified:25 Apr 2018 10:11
Deposited On:26 Apr 2013 06:59

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