Nanahoshi M, Nishiuma T, Tsujishita Y, Hara K, Inui S, Sakaguchi N, Yonezawa K
Biosignal Research Center, Kobe University, 1-1 Rokkodai-cho, Nada-ku, Kobe, 657-8501, Japan.
Biochem Biophys Res Commun. 1998 Oct 20;251(2):520-6. doi: 10.1006/bbrc.1998.9493.
Recent studies have revealed that the alpha4 protein, a mammalian homolog of yeast Tap42, is associated with the protein phosphatase 2A catalytic subunit (PP2A-C), however, effects of the association of alpha4 with PP2A-C on its phosphatase activity have not been examined, especially using physiologically relevant substrates in the signaling pathway of mTOR (the mammalian target of rapamycin) protein. Here, we report how this association affects the enzymatic activity of PP2A-C using the recombinant eIF-4E binding protein (4E-BP1) phosphorylated by immunoprecipitated mTOR as a substrate. PP2A-C dephosphorylated 4E-BP1 in vitro. The association of alpha4 and Tap42 with PP2A-C inhibited the phosphatase activity toward 4E-BP1. Rapamycin treatment, however, neither induced restoration of the phosphatase activity of PP2A-C nor caused dissociation of alpha4 and Tap42 from PP2A-C. Our study is the first report to reveal a potential regulatory role of alpha4 and Tap42 to inibit the phosphatase activity of PP2A-C toward the physiologically relevant substrate in the mTOR signaling.
最近的研究表明，α4蛋白是酵母Tap42的哺乳动物同源物，与蛋白磷酸酶2A催化亚基（PP2A-C）相关联。然而，α4与PP2A-C的关联对其磷酸酶活性的影响尚未得到研究，尤其是在雷帕霉素哺乳动物靶点（mTOR）蛋白信号通路中使用生理相关底物进行的研究。在此，我们报告了这种关联如何利用免疫沉淀的mTOR磷酸化的重组真核翻译起始因子4E结合蛋白（4E-BP1）作为底物来影响PP2A-C的酶活性。PP2A-C在体外使4E-BP1去磷酸化。α4和Tap42与PP2A-C的关联抑制了对4E-BP1的磷酸酶活性。然而，雷帕霉素处理既未诱导PP2A-C磷酸酶活性的恢复，也未导致α4和Tap42从PP2A-C上解离。我们的研究是首次揭示α4和Tap42在mTOR信号传导中对抑制PP2A-C对生理相关底物的磷酸酶活性具有潜在调节作用的报告。
