Biosignal Research Center, Kobe University, Kobe 657-8501, Japan.
FEBS Lett. 2013 Sep 17;587(18):2924-9. doi: 10.1016/j.febslet.2013.07.027. Epub 2013 Jul 24.
Target of rapamycin complex 1 (TORC1) has a key role in cellular regulations in response to environmental conditions. In yeast, Tip41 downregulates TORC1 signaling via activation of PP2A phosphatase. We show here that overexpression of TIPRL, a mammalian Tip41, suppressed dephosphorylation of mechanistic TORC1 (mTORC1) substrates under amino acid withdrawal, and knockdown of TIPRL conversely attenuated phosphorylation of those substrates after amino acid refeeding. TIPRL associated with the catalytic subunit of PP2A (PP2Ac), which was required for the TIPRL action on mTORC1 signaling. Collectively, unlike yeast TIP41, TIPRL has a positive effect on mTORC1 signaling through the association with PP2Ac.
雷帕霉素复合物 1（TORC1）在细胞对环境条件的反应中起着关键作用。在酵母中，Tip41 通过激活 PP2A 磷酸酶来下调 TORC1 信号。我们在这里表明，哺乳动物 Tip41 的 TIPRL 的过表达抑制了氨基酸剥夺时机械性 TORC1（mTORC1）底物的去磷酸化，而 TIPRL 的敲低则相反地减弱了氨基酸再喂养后这些底物的磷酸化。TIPRL 与 PP2A 的催化亚基（PP2Ac）相关，这对于 TIPRL 对 mTORC1 信号的作用是必需的。总的来说，与酵母 TIP41 不同，TIPRL 通过与 PP2Ac 的关联对 mTORC1 信号产生正向影响。
