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首页> 外文期刊>Molecular and Cellular Biology >Activation of Phosphatidylinositol 3-Kinase in Response to Interleukin-1 Leads to Phosphorylation and Activation of the NF-κB p65/RelA Subunit
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Activation of Phosphatidylinositol 3-Kinase in Response to Interleukin-1 Leads to Phosphorylation and Activation of the NF-κB p65/RelA Subunit

机译：响应白细胞介素-1的磷脂酰肌醇3-激酶的激活导致磷酸化和NF-κBp65 / RelA亚基的激活。

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The work of Reddy et al. (S. A. Reddy, J. A. Huang, and W. S. Liao, J. Biol. Chem. 272:29167–29173, 1997) reveals that phosphatidylinositol 3-kinase (PI3K) plays a role in transducing a signal from the occupied interleukin-1 (IL-1) receptor to nuclear factor κB (NF-κB), but the underlying mechanism remains to be determined. We have found that IL-1 stimulates interaction of the IL-1 receptor accessory protein with the p85 regulatory subunit of PI3K, leading to the activation of the p110 catalytic subunit. Specific PI3K inhibitors strongly inhibit both PI3K activation and NF-κB-dependent gene expression but have no effect on the IL-1-stimulated degradation of IκBα, the nuclear translocation of NF-κB, or the ability of NF-κB to bind to DNA. In contrast, PI3K inhibitors block the IL-1-stimulated phosphorylation of NF-κB itself, especially the p65/RelA subunit. Furthermore, by using a fusion protein containing the p65/RelA transactivation domain, we found that overexpression of the p110 catalytic subunit of PI3K induces p65/RelA-mediated transactivation and that the specific PI3K inhibitor LY294,002 represses this process. Additionally, the expression of a constitutively activated form of either p110 or the PI3K-activated protein kinase Akt also induces p65/RelA-mediated transactivation. Therefore, IL-1 stimulates the PI3K-dependent phosphorylation and transactivation of NF-κB, a process quite distinct from the liberation of NF-κB from its cytoplasmic inhibitor IκB.
机译：雷迪等人的工作。 （SA Reddy，JA Huang和WS Liao，J. Biol。Chem。272：29167-29173，1997）发现，磷脂酰肌醇3激酶（PI3K）在转导来自白介素1（IL- 1）核因子κB（NF-κB）受体，但其潜在机制尚待确定。我们发现，IL-1刺激IL-1受体辅助蛋白与PI3K的p85调节亚基相互作用，从而导致p110催化亚基的活化。特定的PI3K抑制剂强烈抑制PI3K激活和NF-κB依赖的基因表达，但对IL-1刺激的IκBα降解，NF-κB的核易位或NF-κB与DNA结合的能力没有影响。 。相反，PI3K抑制剂可阻断IL-1刺激的NF-κB自身磷酸化，尤其是p65 / RelA亚基。此外，通过使用包含p65 / RelA反式激活结构域的融合蛋白，我们发现PI3K的p110催化亚基的过表达诱导p65 / RelA介导的反式激活，并且特定的PI3K抑制剂LY294,002抑制了该过程。此外，p110或PI3K激活的蛋白激酶Akt的组成型激活形式的表达也诱导p65 / RelA介导的反式激活。因此，IL-1刺激了PI3K依赖性的NF-κB磷酸化和反式激活，这一过程与从其胞质抑制剂IκB释放NF-κB完全不同。

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