PAS kinase is activated by direct SNF1-dependent phosphorylation and mediates inhibition of TORC1 through the phosphorylation and activation of Pbp1
| Autor: | J. Brady Evans, Bryan D. Badal, Joseph F. Anderson, Andrew D. Mathis, Desiree DeMille, Julianne H. Grose |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Saccharomyces cerevisiae Proteins
Down-Regulation Saccharomyces cerevisiae Mechanistic Target of Rapamycin Complex 1 Protein Serine-Threonine Kinases MAP2K7 Phosphorylation cascade 03 medical and health sciences 0302 clinical medicine Cyclin-dependent kinase Protein phosphorylation Phosphorylation Protein kinase A Molecular Biology 030304 developmental biology Cell Proliferation 0303 health sciences Cyclin-dependent kinase 1 biology TOR Serine-Threonine Kinases fungi Cyclin-dependent kinase 2 Cell Biology Articles Signaling Cell biology Enzyme Activation Glucose Multiprotein Complexes biology.protein Cyclin-dependent kinase complex Carrier Proteins Protein Kinases 030217 neurology & neurosurgery Signal Transduction |
| Zdroj: | Molecular Biology of the Cell |
| ISSN: | 1939-4586 |
| Popis: | The interplay between AMPK, Psk1, and TORC1 reduces cell growth and proliferation when energy is low. This interplay occurs through Snf1-dependent activation of Psk1, followed by phosphorylation of poly(A)-binding protein binding protein 1 (Pbp1) and subsequent inhibitory sequestration of TORC1 to stress granules. We describe the interplay between three sensory protein kinases in yeast: AMP-regulated kinase (AMPK, or SNF1 in yeast), PAS kinase 1 (Psk1 in yeast), and the target of rapamycin complex 1 (TORC1). This signaling cascade occurs through the SNF1-dependent phosphorylation and activation of Psk1, which phosphorylates and activates poly(A)- binding protein binding protein 1 (Pbp1), which then inhibits TORC1 through sequestration at stress granules. The SNF1-dependent phosphorylation of Psk1 appears to be direct, in that Snf1 is necessary and sufficient for Psk1 activation by alternate carbon sources, is required for altered Psk1 protein mobility, is able to phosphorylate Psk1 in vitro, and binds Psk1 via its substrate-targeting subunit Gal83. Evidence for the direct phosphorylation and activation of Pbp1 by Psk1 is also provided by in vitro and in vivo kinase assays, including the reduction of Pbp1 localization at distinct cytoplasmic foci and subsequent rescue of TORC1 inhibition in PAS kinase–deficient yeast. In support of this signaling cascade, Snf1-deficient cells display increased TORC1 activity, whereas cells containing hyperactive Snf1 display a PAS kinase–dependent decrease in TORC1 activity. This interplay between yeast SNF1, Psk1, and TORC1 allows for proper glucose allocation during nutrient depletion, reducing cell growth and proliferation when energy is low. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|