Kanuck M P, Ellsworth J L
Research Institute, Palo Alto Medical Foundation, California 94301, USA.
Life Sci. 1995;57(22):1981-91. doi: 10.1016/0024-3205(95)02198-r.
The role of tyrosine kinase, protein kinase C, cyclic nucleotide- and Ca(2+)-calmodulin-dependent protein kinase second messenger pathways in the induction of LDL receptor gene expression by hepatocyte growth factor (HGF) was studied in the human hepatoma cell line Hep-G2. Incubation with media containing HGF increased the level of LDL receptor mRNA by 6.5-fold. Co-incubation with HGF and either of two tyrosine kinase inhibitors genistein (2.0-20.0 micrograms/ml) and herbimycin A (0.5-500.0 ng/ml) increased the level of LDL receptor mRNA above that observed with HGF alone by 40-60%. Incubation with HGF in the presence of the calmodulin antagonist W7 (10-30 microM) also super-induced the level of LDL receptor mRNA by nearly 230%. The protein kinase C and A inhibitors chelerythrine (0.1-10.0 microM) and H8 (0.5-5.0 microM), respectively, had no significant effects on the induction of LDL receptor mRNA by HGF. Taken together, these data suggest that tyrosine kinase, protein kinases C and A, and Ca(2+)-calmodulin dependent protein kinase activities are not essential for activation of LDL receptor gene expression in Hep-G2 cells by HGF.
在人肝癌细胞系Hep-G2中，研究了酪氨酸激酶、蛋白激酶C、环核苷酸依赖性蛋白激酶和Ca(2+)-钙调蛋白依赖性蛋白激酶第二信使途径在肝细胞生长因子（HGF）诱导低密度脂蛋白（LDL）受体基因表达中的作用。用含HGF的培养基孵育可使LDL受体mRNA水平增加6.5倍。将HGF与两种酪氨酸激酶抑制剂染料木黄酮（2.0 - 20.0微克/毫升）和赫曲霉素A（0.5 - 500.0纳克/毫升）之一共同孵育，可使LDL受体mRNA水平比单独使用HGF时观察到的水平高出40 - 60%。在钙调蛋白拮抗剂W7（10 - 30微摩尔）存在下用HGF孵育也可使LDL受体mRNA水平超诱导近230%。蛋白激酶C和A抑制剂白屈菜红碱（0.1 - 10.0微摩尔）和H8（0.5 - 5.0微摩尔）分别对HGF诱导LDL受体mRNA没有显著影响。综上所述，这些数据表明酪氨酸激酶、蛋白激酶C和A以及Ca(2+)-钙调蛋白依赖性蛋白激酶活性对于HGF激活Hep-G2细胞中LDL受体基因表达不是必需的。
