Gujdár Annamária, Sipeki Szabolcs, Bander Erzsébet, Buday László, Faragó Anna
Department of Medical Chemistry, Molecular Biology and Pathobiochemistry, Semmelweis University, P.O. Box 260, 1444, Budapest, Hungary.
Cell Signal. 2004 Apr;16(4):505-13. doi: 10.1016/j.cellsig.2003.09.009.
Previously, we reported that, in hepatocyte growth factor (HGF)-induced HepG2 cells, protein kinase C (PKC) decreased the duration of intensive Erk1/Erk2 MAP kinase activation. This study shows that the inhibition of PKC enhanced significantly the HGF-induced integrin expression. Beside the prolonged activation of Erk1/Erk2, the activity of phosphatidylinositol 3-kinase (PI 3K) was required for growth factor-induced integrin expression. PI 3-kinase was activated to a higher extent in response to HGF than to epidermal growth factor (EGF), though the activation was transient in both cases. In EGF-induced cells, PI 3K activation was terminated by the loss of phosphotyrosine docking sites for PI 3K. To the contrary, the decrease of PI 3K activation, which followed the HGF-induced increase was not accompanied by the loss of phosphotyrosine docking sites and was prevented by the inhibition of PKC. The negative modulator effects of PKC on integrin expression and PI 3-kinase activation correlated with its ability to limit the HGF-induced motogen response.
此前，我们报道过，在肝细胞生长因子（HGF）诱导的HepG2细胞中，蛋白激酶C（PKC）缩短了细胞外信号调节激酶1/2（Erk1/Erk2）丝裂原活化蛋白激酶强烈激活的持续时间。本研究表明，抑制PKC可显著增强HGF诱导的整合素表达。除了Erk1/Erk2的持续激活外，磷脂酰肌醇3激酶（PI 3K）的活性也是生长因子诱导整合素表达所必需的。与表皮生长因子（EGF）相比，HGF能使PI 3激酶激活至更高水平，不过在两种情况下激活都是短暂的。在EGF诱导的细胞中，PI 3K的激活因PI 3K磷酸酪氨酸对接位点的丧失而终止。相反，HGF诱导的PI 3K激活增加后出现的激活下降，并非伴随着磷酸酪氨酸对接位点的丧失，且可被PKC抑制所阻止。PKC对整合素表达和PI 3激酶激活的负性调节作用，与其限制HGF诱导的促细胞移动反应的能力相关。
