Investigating the effect of target of rapamycin kinase inhibition on the Chlamydomonas reinhardtii phosphoproteome : from known homologs to new targets

Bibliographische Detailangaben
Veröffentlicht in:	The New phytologist. - 1984. - 221(2019), 1 vom: 24. Jan., Seite 247-260
1. Verfasser:	Werth, Emily G (VerfasserIn)
Weitere Verfasser:	McConnell, Evan W, Couso Lianez, Inmaculada, Perrine, Zoee, Crespo, Jose L, Umen, James G, Hicks, Leslie M
Format:	Online-Aufsatz
Sprache:	English
Veröffentlicht:	2019
Zugriff auf das übergeordnete Werk:	The New phytologist
Schlagworte:	Journal Article Research Support, U.S. Gov't, Non-P.H.S. AZD8055 Chlamydomonas Torin1 phosphoproteomics rapamycin target of rapamycin (TOR) 1-(4-(4-propionylpiperazin-1-yl)-3-(trifluoromethyl)phenyl)-9-(quinolin-3-yl)benzo(h)(1,6)naphthyridin-2(1H)-one Morpholines mehr... Naphthyridines Phosphoproteins Plant Proteins Protein Kinase Inhibitors Carotenoids 36-88-4 (5-(2,4-bis((3S)-3-methylmorpholin-4-yl)pyrido(2,3-d)pyrimidin-7-yl)-2-methoxyphenyl)methanol 970JJ37FPW Mechanistic Target of Rapamycin Complex 1 EC 2.7.11.1 TOR Serine-Threonine Kinases Sirolimus W36ZG6FT64

Beschreibung
Zusammenfassung:	© 2018 The Authors. New Phytologist © 2018 New Phytologist Trust. Target of rapamycin (TOR) kinase is a conserved regulator of cell growth whose activity is modulated in response to nutrients, energy and stress. Key proteins involved in the pathway are conserved in the model photosynthetic microalga Chlamydomonas reinhardtii, but the substrates of TOR kinase and downstream signaling network have not been elucidated. Our study provides a new resource for investigating the phosphorylation networks governed by the TOR kinase pathway in Chlamydomonas. We used quantitative phosphoproteomics to investigate the effects of inhibiting Chlamydomonas TOR kinase on dynamic protein phosphorylation. Wild-type and AZD-insensitive Chlamydomonas strains were treated with TOR-specific chemical inhibitors (rapamycin, AZD8055 and Torin1), after which differentially affected phosphosites were identified. Our quantitative phosphoproteomic dataset comprised 2547 unique phosphosites from 1432 different proteins. Inhibition of TOR kinase caused significant quantitative changes in phosphorylation at 258 phosphosites, from 219 unique phosphopeptides. Our results include Chlamydomonas homologs of TOR signaling-related proteins, including a site on RPS6 with a decrease in phosphorylation. Additionally, phosphosites on proteins involved in translation and carotenoid biosynthesis were identified. Follow-up experiments guided by these phosphoproteomic findings in lycopene beta/epsilon cyclase showed that carotenoid levels are affected by TORC1 inhibition and carotenoid production is under TOR control in algae
Beschreibung:	Date Completed 21.01.2020 Date Revised 04.12.2021 published: Print-Electronic Citation Status MEDLINE
ISSN:	1469-8137
DOI:	10.1111/nph.15339