Molecular Cell Biology, Paul Scherrer Institut, Villigen, Switzerland.
J Cell Mol Med. 2011 Feb;15(2):307-15. doi: 10.1111/j.1582-4934.2009.00967.x.
Charcot-Marie-Tooth disease type 4B is caused by mutations in the genes encoding either the lipid phosphatase myotubularin-related protein-2 (MTMR2) or its regulatory binding partner MTMR13/SBF2. Mtmr2 dephosphorylates PI-3-P and PI-3,5-P2 to form phosphatidylinositol and PI-5-P, respectively, while Mtmr13/Sbf2 is an enzymatically inactive member of the myotubularin protein family. We have found altered levels of the critical signalling protein AKT in mouse mutants for Mtmr2 and Mtmr13/Sbf2. Thus, we analysed the influence of Mtmr2 and Mtmr13/Sbf2 on signalling processes. We found that overexpression of Mtmr2 prevents the degradation of the epidermal growth factor receptor (EGFR) and leads to sustained Akt activation whereas Erk activation is not affected. Mtmr13/Sbf2 counteracts the blockage of EGFR degradation without affecting prolonged Akt activation. Our data indicate that Mtmr2 and Mtmr13/Sbf2 play critical roles in the sorting and modulation of cellular signalling which are likely to be disturbed in CMT4B.
CMT4B 由编码脂质磷酸酶肌管相关蛋白-2 (MTMR2) 或其调节结合伴侣 MTMR13/SBF2 的基因突变引起。Mtmr2 将 PI-3-P 和 PI-3,5-P2 去磷酸化为磷脂和 PI-5-P，而 Mtmr13/Sbf2 是肌管蛋白家族中一种酶失活的成员。我们发现 Mtmr2 和 Mtmr13/Sbf2 小鼠突变体中的关键信号蛋白 AKT 水平发生改变。因此，我们分析了 Mtmr2 和 Mtmr13/Sbf2 对信号转导过程的影响。我们发现，Mtmr2 的过表达可防止表皮生长因子受体 (EGFR) 的降解，并导致 Akt 的持续激活，而 Erk 的激活不受影响。Mtmr13/Sbf2 可阻止 EGFR 降解的阻断，而不影响 Akt 的持续激活。我们的数据表明，Mtmr2 和 Mtmr13/Sbf2 在细胞信号的分拣和调节中发挥关键作用，这可能在 CMT4B 中受到干扰。
