Publication Date:
2013-02-23
Description:
The Ser-Thr kinase mammalian target of rapamycin (mTOR) controls cell growth and metabolism by stimulating glycolysis and synthesis of proteins and lipids. To further understand the central role of mTOR in cell physiology, we used quantitative phosphoproteomics to identify substrates or downstream effectors of the two mTOR complexes. mTOR controlled the phosphorylation of 335 proteins, including CAD (carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase). CAD catalyzes the first three steps in de novo pyrimidine synthesis. mTORC1 indirectly phosphorylated CAD-S1859 through S6 kinase (S6K). CAD-S1859 phosphorylation promoted CAD oligomerization and thereby stimulated de novo synthesis of pyrimidines and progression through S phase of the cell cycle in mammalian cells. Thus, mTORC1 also stimulates the synthesis of nucleotides to control cell proliferation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Robitaille, Aaron M -- Christen, Stefan -- Shimobayashi, Mitsugu -- Cornu, Marion -- Fava, Luca L -- Moes, Suzette -- Prescianotto-Baschong, Cristina -- Sauer, Uwe -- Jenoe, Paul -- Hall, Michael N -- New York, N.Y. -- Science. 2013 Mar 15;339(6125):1320-3. doi: 10.1126/science.1228771. Epub 2013 Feb 21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Biozentrum, University of Basel, Basel, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23429704" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Aspartate Carbamoyltransferase/genetics/*metabolism
;
Carbamoyl-Phosphate Synthase (Glutamine-Hydrolyzing)/genetics/*metabolism
;
Cells, Cultured
;
Dihydroorotase/genetics/*metabolism
;
HeLa Cells
;
Humans
;
Mice
;
Mice, Knockout
;
Multiprotein Complexes/*metabolism
;
Phosphoproteins/*metabolism
;
Proteome/metabolism
;
Pyrimidines/*biosynthesis
;
TOR Serine-Threonine Kinases/*metabolism
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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