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RESEARCH PRODUCT
Serine- and Threonine/Valine-Dependent Activation of PDK and Tor Orthologs Converge on Sch9 to Promote Aging
Min WeiMario G. MirisolaPaola FabrizioValter D. LongoGiusi TaorminaJia-li Husubject
ThreonineCancer ResearchAgingSerineMice0302 clinical medicineSettore BIO/13 - Biologia ApplicataGene Expression Regulation FungalMolecular Cell BiologySerineSignaling in Cellular ProcessesThreonineGenetics (clinical)Cellular Stress Responses0303 health sciencesageing longevity Sch9 Tor Pkhs nutrients amino acidssurvival stress resistanceMechanisms of Signal TransductionValineCell biologyBiochemistryPhosphorylationSignal transductionResearch ArticleSignal TransductionSaccharomyces cerevisiae Proteinslcsh:QH426-470Adenylyl Cyclase Signaling PathwayLongevityP70-S6 Kinase 1Ras SignalingSaccharomyces cerevisiaeBiologyMicrobiologySignaling Pathways3-Phosphoinositide-Dependent Protein Kinases03 medical and health sciencesModel OrganismsStress PhysiologicalGeneticsAnimalsGene NetworksProtein kinase AMolecular BiologyTranscription factorBiologyEcology Evolution Behavior and Systematics030304 developmental biologySerine/threonine-specific protein kinase[SDV.GEN]Life Sciences [q-bio]/GeneticsCyclic AMP-Dependent Protein Kinaseslcsh:GeneticsGlucoseFoodTor SignalingProtein Kinases030217 neurology & neurosurgeryTranscription Factorsdescription
Dietary restriction extends longevity in organisms ranging from bacteria to mice and protects primates from a variety of diseases, but the contribution of each dietary component to aging is poorly understood. Here we demonstrate that glucose and specific amino acids promote stress sensitization and aging through the differential activation of the Ras/cAMP/PKA, PKH1/2 and Tor/S6K pathways. Whereas glucose sensitized cells through a Ras-dependent mechanism, threonine and valine promoted cellular sensitization and aging primarily by activating the Tor/S6K pathway and serine promoted sensitization via PDK1 orthologs Pkh1/2. Serine, threonine and valine activated a signaling network in which Sch9 integrates TORC1 and Pkh signaling via phosphorylation of threonines 570 and 737 and promoted intracellular relocalization and transcriptional inhibition of the stress resistance protein kinase Rim15. Because of the conserved pro-aging role of nutrient and growth signaling pathways in higher eukaryotes, these results raise the possibility that similar mechanisms contribute to aging in mammals.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2014-02-06 |