Ubiquitination of the bacterial inositol phosphatase, SopB, regulates its biological activity at the plasma membrane.
Ubiquitination of the bacterial inositol phosphatase, SopB, regulates its biological activity at the plasma membrane.
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DOI：
10.1111/j.1462-5822.2009.01356.x
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发表时间：
2009-11
影响因子：
3.4
通讯作者：
Steele-Mortimer O
中科院分区：
文献类型：
--
作者：
Knodler LA;Winfree S;Drecktrah D;Ireland R;Steele-Mortimer O
沙门氏菌III型效应子SopB是一种肌醇多磷酸酶，可调节宿主细胞质膜和新生含沙门氏菌液泡（SCV）的磷脂。易位的SopB在感染后持续数小时，并被泛素化，但这种共价修饰的意义尚未研究。在这里，我们通过质谱鉴定六个赖氨酸残基的SopB是单泛素化。用精氨酸取代这六个赖氨酸残基（SopB-K6 R）几乎完全消除了SopB的遍在蛋白化。我们发现，泛素化不影响SopB的稳定性或膜协会，或SopB依赖的事件在SCV的生物发生。然而，两个空间和时间上不同的事件是依赖于泛素化，下调的SopB活性在质膜和延长保留的SopB上的SCV。哺乳动物促生存激酶Akt/PKB（SopB的下游靶点）的激活在感染SopB-K6 R突变体后增强并延长。后来，与SopB相比，用SopB-K6 R修饰的SCV更少。相反，SopB-K6 R作为分散的囊泡在整个细胞中扩散。总之，我们的数据表明，泛素化的SopB是不相关的，其细胞内的稳定性，而是调节其酶活性在质膜和细胞内定位。
The Salmonella type III effector, SopB, is an inositol polyphosphate phosphatase that modulates host cell phospholipids at the plasma membrane and the nascent Salmonella-containing vacuole (SCV). Translocated SopB persists for many hours after infection and is ubiquitinated but the significance of this covalent modification has not been investigated. Here we identify by mass spectrometry six lysine residues of SopB that are mono-ubiquitinated. Substitution of these six lysine residues with arginine, SopB-K6R, almost completely eliminated SopB ubiquitination. We found that ubiquitination does not affect SopB stability or membrane association, or SopB-dependent events in SCV biogenesis. However, two spatially and temporally distinct events are dependent on ubiquitination, downregulation of SopB activity at the plasma membrane and prolonged retention of SopB on the SCV. Activation of the mammalian pro-survival kinase Akt/PKB, a downstream target of SopB, was intensified and prolonged after infection with the SopB-K6R mutant. At later times, fewer SCV were decorated with SopB-K6R compared with SopB. Instead SopB-K6R was present as discrete vesicles spread diffusely throughout the cell. Altogether, our data show that ubiquitination of SopB is not related to its intracellular stability but rather regulates its enzymatic activity at the plasma membrane and intracellular localization.
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DOI：
10.1083/jcb.93.1.97
发表时间：
1982-04
期刊：
The Journal of cell biology
影响因子：
--
作者：
Fujiki Y;Hubbard AL;Fowler S;Lazarow PB
通讯作者：
Lazarow PB
影响因子：
6.7
作者：
Angot, Aurelie;Vergunst, Annette;Genin, Stephane;Peeters, Nemo
通讯作者：
Peeters, Nemo
影响因子：
3.1
作者：
Garcia, Julie Torruellas;Ferracci, Franco;Plano, Gregory V.
通讯作者：
Plano, Gregory V.
影响因子：
3.7
作者：
Ai, Jing;Druhan, Lawrence J.;Avalos, Belinda R.
通讯作者：
Avalos, Belinda R.
影响因子：
3.1
作者：
ALLAOUI, A;MENARD, R;PARSOT, C
通讯作者：
PARSOT, C