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The Tor and PKA signaling pathways independently target the Atg1/Atg13 protein kinase complex to control autophagy

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dc.contributor.author Stephan, Joseph S.
dc.contributor.author Yeh, Yuh-Ying
dc.contributor.author Ramachandran, Vidhya
dc.contributor.author Deminoff, Stephen J.
dc.date.accessioned 2017-09-22T08:19:41Z
dc.date.available 2017-09-22T08:19:41Z
dc.date.copyright 2009 en_US
dc.identifier.uri http://hdl.handle.net/10725/6234
dc.description.abstract Macroautophagy (or autophagy) is a conserved degradative pathway that has been implicated in a number of biological processes, including organismal aging, innate immunity, and the progression of human cancers. This pathway was initially identified as a cellular response to nutrient deprivation and is essential for cell survival during these periods of starvation. Autophagy is highly regulated and is under the control of a number of signaling pathways, including the Tor pathway, that coordinate cell growth with nutrient availability. These pathways appear to target a complex of proteins that contains the Atg1 protein kinase. The data here show that autophagy in Saccharomyces cerevisiae is also controlled by the cAMP-dependent protein kinase (PKA) pathway. Elevated levels of PKA activity inhibited autophagy and inactivation of the PKA pathway was sufficient to induce a robust autophagy response. We show that in addition to Atg1, PKA directly phosphorylates Atg13, a conserved regulator of Atg1 kinase activity. This phosphorylation regulates Atg13 localization to the preautophagosomal structure, the nucleation site from which autophagy pathway transport intermediates are formed. Atg13 is also phosphorylated in a Tor-dependent manner, but these modifications appear to occur at positions distinct from the PKA phosphorylation sites identified here. In all, our data indicate that the PKA and Tor pathways function independently to control autophagy in S. cerevisiae, and that the Atg1/Atg13 kinase complex is a key site of signal integration within this degradative pathway. en_US
dc.language.iso en en_US
dc.publisher National Academy of Sciences of the United States of America en_US
dc.title The Tor and PKA signaling pathways independently target the Atg1/Atg13 protein kinase complex to control autophagy en_US
dc.type Conference Paper / Proceeding en_US
dc.author.school SOM en_US
dc.author.idnumber 201509224 en_US
dc.author.department N/A en_US
dc.description.embargo N/A en_US
dc.keywords CAMP-dependent protein kinase en_US
dc.keywords Macroautophagy en_US
dc.keywords Stationary phase en_US
dc.keywords Tor protein kinase en_US
dc.identifier.doi http://dx.doi.org/10.1073/pnas.0903316106 en_US
dc.identifier.ctation Stephan, J. S., Yeh, Y. Y., Ramachandran, V., Deminoff, S. J., & Herman, P. K. (2009). The Tor and PKA signaling pathways independently target the Atg1/Atg13 protein kinase complex to control autophagy. Proceedings of the National Academy of Sciences, 106(40), 17049-17054. en_US
dc.author.email joseph.stephan@lau.edu.lb en_US
dc.identifier.tou http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.php en_US
dc.identifier.url http://www.pnas.org/content/106/40/17049.short en_US
dc.author.affiliation Lebanese American University en_US
dc.relation.numberofseries 106 en_US
dc.title.volume Proceedings of the National Academy of Sciences of the United States of America en_US


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