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PMID: 20439775 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Autophosphorylation within the Atg1 activation loop is required for both kinase activity and the induction of autophagy in Saccharomyces cerevisiae.

Genetics ·Vol. 185 ·No. 3 ·2010-07-00 ·Pages 871-82

Yeh YY, Wrasman K, Herman PK

Abstract

Autophagy is an evolutionarily conserved degradative pathway that has been implicated in a number of physiological events important for human health. This process was originally identified as a response to nutrient deprivation and is thought to serve in a recycling capacity during periods of nutritional stress. Autophagy activity appears to be highly regulated and multiple signaling pathways are known to target a complex of proteins that contains the Atg1 protein kinase. The data here extend these observations and identify a particular phosphorylation event on Atg1 as a potential control point within the autophagy pathway in Saccharomyces cerevisiae. This phosphorylation occurs at a threonine residue, T226, within the Atg1 activation loop that is conserved in all Atg1 orthologs. Replacing this threonine with a nonphosphorylatable residue resulted in a loss of Atg1 protein kinase activity and a failure to induce autophagy. This phosphorylation required the presence of a functional Atg1 kinase domain and two known regulators of Atg1 activity, Atg13 and Atg17. Interestingly, the levels of this modification were found to increase dramatically upon exposure to conditions that induce autophagy. In addition, T226 phosphorylation was associated with an autophosphorylated form of Atg1 that was found specifically in cells undergoing the autophagy process. In all, these data suggest that autophosphorylation within the Atg1 activation loop may represent a point of regulatory control for this degradative process.

MeSH Terms
Adaptor Proteins, Signal Transducing/genetics,metabolism Amino Acid Sequence Autophagy Autophagy-Related Proteins Blotting, Western Carrier Proteins/genetics,metabolism Immunoprecipitation Molecular Sequence Data Mutation/genetics Phosphorylation Protein Kinases/genetics,metabolism Saccharomyces cerevisiae/genetics,growth & development,metabolism Saccharomyces cerevisiae Proteins/genetics,metabolism Sequence Homology, Amino Acid Signal Transduction
Chemicals
ATG13 protein, S cerevisiae Adaptor Proteins, Signal Transducing Atg17 protein, S cerevisiae Autophagy-Related Proteins Carrier Proteins Saccharomyces cerevisiae Proteins Protein Kinases ATG1 protein, S cerevisiae
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Yeh Yuh-Ying
Department of Molecular Genetics, The Ohio State University, Columbus Ohio 43210, USA.
Wrasman Kristie
Herman Paul K
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Article Info
Journal
Genetics
Abbr.
Genetics
ISSN
1943-2631
DOI
10.1534/genetics.110.116566
Published
2010-07-00
Epub
2010-00-03
Pages
871-82
Language
English
Region
United States
NLM ID
0374636
PMCID
PMC2907206
Subset
IM
Grants
NIGMS NIH HHS · R01 GM065227 · United States
NIGMS NIH HHS · GM65227 · United States
External Links
PubMed source DOI: 10.1534/genetics.110.116566 PMC Full Text View journal details
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