The regulation of Atg1 protein kinase activity is important to the autophagy process in <i>Saccharomyces cerevisiae</i>
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| Language: | English |
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The Ohio State University / OhioLINK
2010
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| Online Access: | http://rave.ohiolink.edu/etdc/view?acc_num=osu1290439442 |
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ndltd-OhioLink-oai-etd.ohiolink.edu-osu1290439442 |
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oai_dc |
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NDLTD |
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English |
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NDLTD |
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Cellular Biology Genetics Molecular Biology Autophagy Atg1 protein kinase Atg1 protein complex Activation loop phosphorylation Glycine-rich loop |
| spellingShingle |
Cellular Biology Genetics Molecular Biology Autophagy Atg1 protein kinase Atg1 protein complex Activation loop phosphorylation Glycine-rich loop Yeh, Yuh-Ying The regulation of Atg1 protein kinase activity is important to the autophagy process in <i>Saccharomyces cerevisiae</i> |
| author |
Yeh, Yuh-Ying |
| author_facet |
Yeh, Yuh-Ying |
| author_sort |
Yeh, Yuh-Ying |
| title |
The regulation of Atg1 protein kinase activity is important to the autophagy process in <i>Saccharomyces cerevisiae</i> |
| title_short |
The regulation of Atg1 protein kinase activity is important to the autophagy process in <i>Saccharomyces cerevisiae</i> |
| title_full |
The regulation of Atg1 protein kinase activity is important to the autophagy process in <i>Saccharomyces cerevisiae</i> |
| title_fullStr |
The regulation of Atg1 protein kinase activity is important to the autophagy process in <i>Saccharomyces cerevisiae</i> |
| title_full_unstemmed |
The regulation of Atg1 protein kinase activity is important to the autophagy process in <i>Saccharomyces cerevisiae</i> |
| title_sort |
regulation of atg1 protein kinase activity is important to the autophagy process in <i>saccharomyces cerevisiae</i> |
| publisher |
The Ohio State University / OhioLINK |
| publishDate |
2010 |
| url |
http://rave.ohiolink.edu/etdc/view?acc_num=osu1290439442 |
| work_keys_str_mv |
AT yehyuhying theregulationofatg1proteinkinaseactivityisimportanttotheautophagyprocessinisaccharomycescerevisiaei AT yehyuhying regulationofatg1proteinkinaseactivityisimportanttotheautophagyprocessinisaccharomycescerevisiaei |
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1719429460433829888 |
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ndltd-OhioLink-oai-etd.ohiolink.edu-osu12904394422021-08-03T06:01:01Z The regulation of Atg1 protein kinase activity is important to the autophagy process in <i>Saccharomyces cerevisiae</i> Yeh, Yuh-Ying Cellular Biology Genetics Molecular Biology Autophagy Atg1 protein kinase Atg1 protein complex Activation loop phosphorylation Glycine-rich loop <p>Autophagy is an evolutionarily conserved, degradative pathway that has been implicatedin a number of physiological processes such as development and aging as well as cancerand innate immunity. This pathway is important for cell survival in starvation and isconsidered as a potential target for therapeutic intervention in a number of pathologicalconditions. Therefore, it is important that we develop a thorough understanding of themechanisms regulating this trafficking pathway. Autophagy was initially identified as acellular response to nutrient deprivation and is essential for cell survival during periods ofstarvation. During autophagy, an isolation membrane emanates from a nucleation site thatis known as the phagophore assembly site (PAS). This membrane encapsulates nearbycytoplasm to form an autophagosome that is ultimately targeted to the vacuole/lysosomefor degradation. The small molecules produced are then recycled and used by cells duringthis period of starvation. Autophagy activity is highly regulated and multiple signalingpathways are known to target a complex of proteins that contains the Atg1 protein kinase.</p><p>Atg1 protein kinase activity is essential for normal autophagy in all eukaryotesand appears to be controlled tightly by a number of kinases, which target this enzyme andits associated protein partners. Our data and that of others have established that Atg1activity is regulated, at least in part, by protein phosphorylation. In this work, weidentified a particular phosphorylation event on Atg1 as an important control point within the autophagy pathway in <i>Saccharomyces cerevisiae</i>. This phosphorylation occurs at athreonine residue, T226, within the Atg1 activation loop that is conserved in all Atg1orthologs. This activation loop phosphorylation is essential for Atg1 kinase activity andthe induction of autophagy. The data also suggested that promoting thisautophosphorylation is a primary role for two key conserved regulators of Atg1 activity,Atg13 and Atg17. Atg13, in particular, appears to stimulate this phosphorylation bypromoting an Atg1 self-interaction. In all, these data suggest that autophosphorylationwithin the Atg1 activation loop may represent a point of regulatory control for thisdegradative process.</p><p>To further our knowledge of phosphorylation in Atg1, we used a combined massspectrometry and molecular biology approach to identify and characterize additional sitesof phosphorylation in Atg1. Fifteen sites of phosphorylation were discovered here,including nine that had not been noted previously. Alterations of these sites identified anumber of positions that appear to be important for full autophagy activity <i>in vivo</i>. Onesite was of special interest as it was within a highly conserved motif, the Gly-rich loop, inthe Atg1 kinase domain. Phosphorylation at this equivalent position inhibits the kinaseactivity of particular cyclin-dependent kinases and we showed here that this site mayserve a similar function in Atg1. In addition, we identified Ser-390 as the site ofautophosphorylation responsible for the anomalous migration observed for Atg1 on SDSpolyacrylamidegels. In all, the analyses here identified a number of potential sites ofregulation in the Atg1 protein that provide important insight into the control of theautophagy process and will form a framework for future studies with this enzyme.</p> 2010-12-15 English text The Ohio State University / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=osu1290439442 http://rave.ohiolink.edu/etdc/view?acc_num=osu1290439442 unrestricted This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws. |