The regulatory subunits of PI3K, p85α and p85β, differentially affect BRD7-mediated regulation of insulin signaling.
The regulatory subunits of PI3K, p85α and p85β, differentially affect BRD7-mediated regulation of insulin signaling.
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PI3K的调节亚基p85α和p85β对BRD7介导的胰岛素信号传导调节的影响不同。
DOI：
10.1093/jmcb/mjab073
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发表时间：
2022-01-29
影响因子：
5.5
通讯作者：
Park SW
中科院分区：
文献类型：
--
作者：
Lee JM;Liu R;Park SW
含溴结构域蛋白7（BRD 7）已被证明在胰岛素信号传导途径中与磷脂酰肌醇3-激酶（PI 3 K）的调节亚基p85相互作用。在这里，我们发现，上调肝脏BRD 7改善葡萄糖稳态，即使在没有任何p85亚型，p85α或p85β。然而，BRD 7导致胰岛素信号传导途径中下游效应蛋白的差异活化，这取决于存在哪种p85亚型。在仅存在p85α的情况下，BRD 7过表达增加胰岛素刺激后胰岛素受体（IR）的磷酸化，而不增加p85向IR底物的募集。BRD 7的过表达还增加了Akt对胰岛素的响应激活，但不影响Akt的基础磷酸化水平。同时，糖原合成酶激酶3β（GSK 3 β）的磷酸化通过BRD 7的过表达而增加。另一方面，在仅存在p85β的情况下，BRD 7过表达不影响IR的磷酸化水平，并且Akt磷酸化不受BRD 7上调后胰岛素刺激的影响。然而，BRD 7过表达导致Akt和GSK 3 β的基础磷酸化水平增加。这些数据表明，BRD 7对葡萄糖稳态的作用不需要两种p85亚型的存在，并且p85α和p85β在肝脏中的胰岛素信号传导中具有独特的作用。
Bromodomain-containing protein 7 (BRD7) has been shown to interact with the regulatory subunit of phosphatidylinositol 3-kinase (PI3K), p85, in the insulin signaling pathway. Here, we show that upregulation of hepatic BRD7 improves glucose homeostasis even in the absence of either p85 isoform, p85α or p85β. However, BRD7 leads to differential activation of downstream effector proteins in the insulin signaling pathway depending on which isoform of p85 is present. In the presence of only p85α, BRD7 overexpression increases phosphorylation of insulin receptor (IR) upon insulin stimulation, without increasing the recruitment of p85 to IR substrate. Overexpression of BRD7 also increases activation of Akt in response to insulin, but does not affect basal phosphorylation levels of Akt. Meanwhile, the phosphorylation of glycogen synthase kinase 3β (GSK3β) is increased by overexpression of BRD7. On the other hand, in the presence of only p85β, BRD7 overexpression does not affect phosphorylation levels of IR, and Akt phosphorylation is not affected by insulin stimulation following BRD7 upregulation. However, BRD7 overexpression leads to increased basal phosphorylation levels of Akt and GSK3β. These data demonstrate that BRD7’s action on glucose homeostasis does not require the presence of both p85 isoforms, and p85α and p85β have unique roles in insulin signaling in the liver.
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影响因子：
7.7
作者：
Cheung LW;Walkiewicz KW;Besong TM;Guo H;Hawke DH;Arold ST;Mills GB
通讯作者：
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10.1073/pnas.1322564111
发表时间：
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影响因子：
11.1
作者：
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通讯作者：
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