title: PAS kinase is activated by direct SNF1-dependent phosphorylation and mediates inhibition of TORC1 through the phosphorylation and activation of Pbp1.
abstract: 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.
authors.affiliation: Department of Microbiology and Molecular Biology, Brigham Young University, Provo, UT 84602.
authors.forename: Desiree
authors.initials: D
authors.lastname: DeMille
authors.affiliation: Department of Microbiology and Molecular Biology, Brigham Young University, Provo, UT 84602.
authors.forename: Bryan D
authors.initials: BD
authors.lastname: Badal
authors.affiliation: Department of Microbiology and Molecular Biology, Brigham Young University, Provo, UT 84602.
authors.forename: J Brady
authors.initials: JB
authors.lastname: Evans
authors.affiliation: Department of Chemistry, Brigham Young University, Provo, UT 84602.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Mathis
authors.affiliation: Department of Microbiology and Molecular Biology, Brigham Young University, Provo, UT 84602.
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Anderson
authors.affiliation: Department of Microbiology and Molecular Biology, Brigham Young University, Provo, UT 84602 julianne_grose@byu.edu.
authors.forename: Julianne H
authors.initials: JH
authors.lastname: Grose
mesh_terms: D002352:Carrier Proteins / Q000378:metabolism*; D049109:Cell Proliferation; D015536:Down-Regulation; D004789:Enzyme Activation; D005947:Glucose / Q000378:metabolism*; D000076222:Mechanistic Target of Rapamycin Complex 1; D046912:Multiprotein Complexes / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000254:growth & development / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D046912:Multiprotein Complexes; C116076:PBP1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D011494:Protein Kinases; C467888:PSK1 protein, S cerevisiae; C071570:SNF1-related protein kinases; D000076222:Mechanistic Target of Rapamycin Complex 1; D017346:Protein Serine-Threonine Kinases; D058570:TOR Serine-Threonine Kinases; D005947:Glucose