The Tor and PKA signaling pathways independently target the Atg1/Atg13 protein kinase complex to control autophagy
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 i...
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2009
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| Online Access: | http://hdl.handle.net/10725/6234 http://dx.doi.org/10.1073/pnas.0903316106 http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.php http://www.pnas.org/content/106/40/17049.short |
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| _version_ | 1864513478935445504 |
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| author | Stephan, Joseph S. |
| author2 | Yeh, Yuh-Ying Ramachandran, Vidhya Deminoff, Stephen J. |
| author2_role | author author author |
| author_facet | Stephan, Joseph S. Yeh, Yuh-Ying Ramachandran, Vidhya Deminoff, Stephen J. |
| author_role | author |
| dc.creator.none.fl_str_mv | Stephan, Joseph S. Yeh, Yuh-Ying Ramachandran, Vidhya Deminoff, Stephen J. |
| dc.date.none.fl_str_mv | 2009 2017-09-22T08:19:41Z 2017-09-22T08:19:41Z 2017-09-22 |
| dc.identifier.none.fl_str_mv | http://hdl.handle.net/10725/6234 http://dx.doi.org/10.1073/pnas.0903316106 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. http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.php http://www.pnas.org/content/106/40/17049.short |
| dc.language.none.fl_str_mv | en |
| dc.publisher.none.fl_str_mv | National Academy of Sciences of the United States of America |
| dc.relation.none.fl_str_mv | 106 |
| dc.rights.*.fl_str_mv | info:eu-repo/semantics/openAccess |
| dc.title.none.fl_str_mv | The Tor and PKA signaling pathways independently target the Atg1/Atg13 protein kinase complex to control autophagy Proceedings of the National Academy of Sciences of the United States of America |
| dc.type.none.fl_str_mv | Conference Paper / Proceeding info:eu-repo/semantics/publishedVersion info:eu-repo/semantics/conferenceObject |
| description | 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. |
| eu_rights_str_mv | openAccess |
| format | conferenceObject |
| id | LAURepo_fb9a956f78e93d2382aebd950f8052c3 |
| identifier_str_mv | 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. |
| language_invalid_str_mv | en |
| network_acronym_str | LAURepo |
| network_name_str | Lebanese American University repository |
| oai_identifier_str | oai:laur.lau.edu.lb:10725/6234 |
| publishDate | 2009 |
| publisher.none.fl_str_mv | National Academy of Sciences of the United States of America |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| spelling | The Tor and PKA signaling pathways independently target the Atg1/Atg13 protein kinase complex to control autophagyProceedings of the National Academy of Sciences of the United States of AmericaStephan, Joseph S.Yeh, Yuh-YingRamachandran, VidhyaDeminoff, Stephen J.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.N/ANational Academy of Sciences of the United States of America2017-09-22T08:19:41Z2017-09-22T08:19:41Z20092017-09-22Conference Paper / Proceedinginfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjecthttp://hdl.handle.net/10725/6234http://dx.doi.org/10.1073/pnas.0903316106Stephan, 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.http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.phphttp://www.pnas.org/content/106/40/17049.shorten106info:eu-repo/semantics/openAccessoai:laur.lau.edu.lb:10725/62342021-03-19T10:43:10Z |
| spellingShingle | The Tor and PKA signaling pathways independently target the Atg1/Atg13 protein kinase complex to control autophagy Stephan, Joseph S. |
| status_str | publishedVersion |
| title | The Tor and PKA signaling pathways independently target the Atg1/Atg13 protein kinase complex to control autophagy |
| title_full | The Tor and PKA signaling pathways independently target the Atg1/Atg13 protein kinase complex to control autophagy |
| title_fullStr | The Tor and PKA signaling pathways independently target the Atg1/Atg13 protein kinase complex to control autophagy |
| title_full_unstemmed | The Tor and PKA signaling pathways independently target the Atg1/Atg13 protein kinase complex to control autophagy |
| title_short | The Tor and PKA signaling pathways independently target the Atg1/Atg13 protein kinase complex to control autophagy |
| title_sort | The Tor and PKA signaling pathways independently target the Atg1/Atg13 protein kinase complex to control autophagy |
| url | http://hdl.handle.net/10725/6234 http://dx.doi.org/10.1073/pnas.0903316106 http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.php http://www.pnas.org/content/106/40/17049.short |