Activation of Akt by the bacterial inositol phosphatase, SopB, is wortmannin insensitive.
Activation of Akt by the bacterial inositol phosphatase, SopB, is wortmannin insensitive.
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DOI：
10.1371/journal.pone.0022260
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Steele-Mortimer O
中科院分区：
文献类型：
--
作者：
Cooper KG;Winfree S;Malik-Kale P;Jolly C;Ireland R;Knodler LA;Steele-Mortimer O
肠道沙门氏菌利用III型分泌系统转运的效应蛋白侵入上皮细胞。侵袭相关效应物之一SopB是肌醇磷酸酶，其介导受感染细胞中促存活激酶Akt的持续活化。Akt的典型激活涉及膜转位和磷酸化，并且依赖于磷脂酰肌醇3激酶（PI3K）。在这里，我们研究了这两个不同的过程中沙门氏菌感染的HeLa细胞。首先，我们发现SopB依赖的膜转位和Akt的磷酸化对PI3K抑制剂wortmannin不敏感。同样，通过RNAi去除PI3K调节亚基p85 α和p85 β对SopB依赖性Akt磷酸化没有抑制作用。然而，SopB依赖性磷酸化确实依赖于Akt激酶、PDK1和rictor-mTOR。膜易位试验揭示了依赖于SopB的Akt招募沙门氏菌皱褶，并表明这是由磷酸肌醇（3，4）P2，而不是磷酸肌醇（3，4，5）P3介导的。总之，这些数据表明沙门氏菌通过渥曼青霉素不敏感机制激活Akt，该机制可能是I类PI3K非依赖性过程，其结合了经典途径的一些基本要素。
Salmonella enterica uses effector proteins translocated by a Type III Secretion System to invade epithelial cells. One of the invasion-associated effectors, SopB, is an inositol phosphatase that mediates sustained activation of the pro-survival kinase Akt in infected cells. Canonical activation of Akt involves membrane translocation and phosphorylation and is dependent on phosphatidyl inositide 3 kinase (PI3K). Here we have investigated these two distinct processes in Salmonella infected HeLa cells. Firstly, we found that SopB-dependent membrane translocation and phosphorylation of Akt are insensitive to the PI3K inhibitor wortmannin. Similarly, depletion of the PI3K regulatory subunits p85α and p85ß by RNAi had no inhibitory effect on SopB-dependent Akt phosphorylation. Nevertheless, SopB-dependent phosphorylation does depend on the Akt kinases, PDK1 and rictor-mTOR. Membrane translocation assays revealed a dependence on SopB for Akt recruitment to Salmonella ruffles and suggest that this is mediated by phosphoinositide (3,4) P2 rather than phosphoinositide (3,4,5) P3. Altogether these data demonstrate that Salmonella activates Akt via a wortmannin insensitive mechanism that is likely a class I PI3K-independent process that incorporates some essential elements of the canonical pathway.
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