Sipeki S, Bander E, Buday L, Farkas G, Bácsy E, Ways D K, Faragó A
Department of Medical Chemistry, Molecular Biology and Pathobiochemistry, Semmelweis University of Medicine, Budapest, Hungary.
Cell Signal. 1999 Dec;11(12):885-90. doi: 10.1016/s0898-6568(99)00060-1.
MAP kinase cascade-dependent responses were investigated during scattering of HepG2 human hepatoma cells stimulated by HGF or phorbol ester. Inhibition of phosphatidylinositol 3-kinase with LY294002 prevented completely the dissociation of cells. Inhibition of MAP kinase kinase (MEK) with PD98059 prevented the development of characteristic morphological changes associated with cell migration. EGF, which failed to induce cell scattering, caused a short-term increase in the phosphorylation of Erk1/Erk2 MAP kinases. On the contrary, HGF or phorbol ester stimulated the phosphorylation of MAP kinases for a long time. Experiments performed with LY294002 indicated that phosphatidylinositol 3-kinase contributed to the HGF-stimulated phosphorylation of Erk1/Erk2. This finding was confirmed by the demonstration that the MAP kinase cascade-dependent expression of a high-Mr (>300 kDa) protein pair appearing in the course of cell scattering was inhibited by LY294002 in HGF-induced cells but was not inhibited in phorbol ester-treated cells.
在HGF或佛波酯刺激HepG2人肝癌细胞散射过程中，研究了丝裂原活化蛋白激酶（MAP）激酶级联反应依赖性应答。用LY294002抑制磷脂酰肌醇3激酶可完全阻止细胞解离。用PD98059抑制MAP激酶激酶（MEK）可阻止与细胞迁移相关的特征性形态变化的发展。未能诱导细胞散射的表皮生长因子（EGF）导致Erk1/Erk2 MAP激酶磷酸化短期增加。相反，HGF或佛波酯可长时间刺激MAP激酶磷酸化。用LY294002进行的实验表明，磷脂酰肌醇3激酶促进了HGF刺激的Erk1/Erk2磷酸化。这一发现通过以下证明得到证实：在细胞散射过程中出现的高分子量（>300 kDa）蛋白对的MAP激酶级联反应依赖性表达在HGF诱导的细胞中被LY294002抑制，但在佛波酯处理的细胞中未被抑制。
