Abstract:
:The mammalian target of rapamycin (mTOR) is a Ser/Thr (S/T) protein kinase, which controls mRNA translation initiation by modulating phosphorylation of the translational regulators PHAS-I and p70(S6K). Here we show that in vitro mTOR is able to phosphorylate these two regulators at comparable rates. Both (S/T)P sites, such as Thr36, Thr45, and Thr69 in PHAS-I and the h(S/T)h site (where h is a hydrophobic amino acid) Thr389 in p70(S6K), were phosphorylated. Rapamycin-FKBP12 inhibited mTOR activity. Surprisingly, the extent of inhibition depended on the substrate. Moreover, mutating Ser2035 in the rapamycin-binding domain (FRB) not only decreased rapamycin sensitivity as expected but also dramatically affected the sites phosphorylated by mTOR. The results demonstrate that mutations in Ser2035 are not silent with respect to mTOR activity and implicate the FRB in substrate recognition. The findings also impose new limitations on interpreting results from experiments in which rapamycin and/or rapamycin-resistant forms of mTOR are used to investigate mTOR function in cells.
journal_name
Mol Cell Bioljournal_title
Molecular and cellular biologyauthors
McMahon LP,Choi KM,Lin TA,Abraham RT,Lawrence JC Jrdoi
10.1128/mcb.22.21.7428-7438.2002subject
Has Abstractpub_date
2002-11-01 00:00:00pages
7428-38issue
21eissn
0270-7306issn
1098-5549journal_volume
22pub_type
杂志文章abstract::In vitro mutagenesis was used to create putative opal suppressor alleles of a tRNA(Trp) gene of Saccharomyces cerevisiae. The construct with the requisite anticodon change did not result in an active suppressor, whereas when a second change was introduced into the portion of the gene encoding the intron, an active and...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.10.8.4379
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.10.4.1754
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.13.8.4976
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pub_type: 杂志文章
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
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pub_type: 杂志文章
doi:10.1128/mcb.23.15.5122-5131.2003
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pub_type: 杂志文章
doi:10.1128/mcb.5.8.2090
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.6.2.635
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.16.5.2238
更新日期:1996-05-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.10.2.561
更新日期:1990-02-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.02432-06
更新日期:2007-07-01 00:00:00
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pub_type: 杂志文章
doi:10.1128/mcb.22.10.3497-3508.2002
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.10.9.4961
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.5.8.1959
更新日期:1985-08-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00030-07
更新日期:2007-05-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.13.1.668
更新日期:1993-01-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.6.12.4585
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
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pub_type: 杂志文章
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.19.1.155
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abstract::The fission yeast pap1+ gene encodes an AP-1-like transcription factor that contains a leucine zipper motif. We identified a target gene of pap1, the p25 gene. The 5' upstream region of the p25 gene contains an AP-1 site, and by DNase I footprint analysis, we showed that the pap1 protein binds to the AP-1 site as well...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.12.12.5474
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.16.1.390
更新日期:1996-01-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.13.12.7288
更新日期:1993-12-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.4.3.475
更新日期:1984-03-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00898-15
更新日期:2015-11-02 00:00:00