Yoshikawa Kyoko, Nigorikawa Kiyomi, Tsukamoto Mariko, Tamura Namiko, Hazeki Kaoru, Hazeki Osamu
Division of Molecular Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, Minami-ku, Hiroshima 734-8553, Japan.
Biochim Biophys Acta. 2007 Apr;1770(4):687-93. doi: 10.1016/j.bbagen.2006.12.009. Epub 2006 Dec 24.
Menadione (vitamin K(3)) has been shown to activate Erk in several cell lines. This effect has been shown to be due to the activation of EGF receptors (EGFR) as a result of inhibition of some protein tyrosine phosphatases. In the present study, we examined the effects of menadione on Akt in Chinese hamster ovary cells. The phosphorylation of Akt by menadione was not inhibited by AG1478, an inhibitor of EGFR. Menadione inhibited the lipid phosphatase activity of PTEN in a cell-free system. In an intact cell system, menadione inhibited the effect of transfected PTEN on Akt. Thus, one mechanism of its action was considered the accelerated activation of Akt through inhibition of PTEN. This was not the sole mechanism responsible for the EGFR-independent activation of Akt, because menadione attenuated the rate of Akt dephosphorylation even in PTEN-null PC3 cells. The decelerated inactivation of Akt, probably through inhibition of some tyrosine phosphatases, was considered another mechanism of its action.
甲萘醌（维生素K(3)）已被证明能在多种细胞系中激活细胞外调节蛋白激酶（Erk）。这种效应已被证明是由于某些蛋白酪氨酸磷酸酶受到抑制，从而激活了表皮生长因子受体（EGFR）所致。在本研究中，我们检测了甲萘醌对中国仓鼠卵巢细胞中Akt的影响。甲萘醌对Akt的磷酸化作用不受EGFR抑制剂AG1478的抑制。甲萘醌在无细胞体系中抑制了第10号染色体缺失的磷酸酶及张力蛋白同源物（PTEN）的脂质磷酸酶活性。在完整细胞体系中，甲萘醌抑制了转染的PTEN对Akt的作用。因此，其作用机制之一被认为是通过抑制PTEN来加速Akt的激活。但这并非Akt非依赖EGFR激活的唯一机制，因为即使在PTEN基因敲除的PC3细胞中，甲萘醌也能减缓Akt的去磷酸化速率。Akt失活的减缓可能是通过抑制某些酪氨酸磷酸酶实现的，这被认为是其另一种作用机制。
