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p85 Associates with Unphosphorylated PTEN and the PTEN-Associated Complex

机译:p85与未磷酸化的PTEN和PTEN相关的复合物相关

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The lipid phosphatase PTEN functions as a tumor suppressor by dephosphorylating the D3 position of phosphoinositide-3,4,5-trisphosphate, thereby negatively regulating the phosphoinositide 3-kinase (PI3K)/AKT signaling pathway. In mammalian cells, PTEN exists either as a monomer or as a part of a >600-kDa complex (the PTEN-associated complex [PAC]). Previous studies suggest that the antagonism of PI3K/AKT signaling by PTEN may be mediated by a nonphosphorylated form of the protein resident within the multiprotein complex. Here we show that PTEN associates with p85, the regulatory subunit of PI3K. Using newly generated antibodies, we demonstrate that this PTEN-p85 association involves the unphosphorylated form of PTEN engaged within the PAC and also includes the p110β isoform of PI3K. The PTEN-p85 association is enhanced by trastuzumab treatment and linked to a decline in AKT phosphorylation in some ERBB2-amplified breast cancer cell lines. Together, these results suggest that integration of p85 into the PAC may provide a novel means of downregulating the PI3K/AKT pathway.
机译:脂质磷酸酶PTEN通过使3,4,5-三磷酸磷酸肌醇的D3位置去磷酸化,从而起到抑癌作用,从而负调节磷酸肌醇3激酶(PI3K)/ AKT信号通路。在哺乳动物细胞中,PTEN作为单体或> 600 kDa复合物(与PTEN相关的复合物[PAC])的一部分存在。先前的研究表明,PTEN对PI3K / AKT信号的拮抗作用可能是由驻留在多蛋白复合物中的蛋白的非磷酸化形式介导的。在这里,我们显示PTEN与PI3K的调节亚基p85相关。使用新产生的抗体,我们证明了这种PTEN-p85缔合涉及参与PAC的PTEN的未磷酸化形式,还包括PI3K的p110β同种型。通过曲妥珠单抗治疗可以增强PTEN-p85的关联,并与某些 ERBB2 扩增的乳腺癌细胞系中AKT磷酸化的下降有关。在一起,这些结果表明p85整合到PAC中可能提供一种下调PI3K / AKT途径的新颖手段。

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