Topol L Z, Blair D G
Laboratory of Molecular Oncology, National Cancer Institute, Frederick, Maryland 21702-1201, USA.
Cell Growth Differ. 1995 Sep;6(9):1119-27.
We have characterized activation of the MAP kinase cascade in an inducible system in response to the temperature-sensitive (ts) expression of the v-mos oncogene. Transformation of immortalized rat embryo fibroblasts by a ts isolate of Moloney murine sarcoma virus (Mo-MuSVts110) constitutively activates MAP kinases (ERK-1 and ERK-2) and MAP kinase kinases (MKK-1 and MKK-2) only at the permissive temperature when v-mos kinase is present and active. Following a shift of the ts-transformed, serum-starved cells from the nonpermissive to permissive temperature, MAP kinases and both MKK-1 and MKK-2 are activated within 1-2 h, concurrent with the reappearance of active mos kinase. Raf-1 kinase activity increases more slowly in response to the reappearance of v-mos, and the mobility shift indicative of hyperphosphorylation was only detected 18 h after the temperature transition. Our data show that MAP kinase cascade activation is an early event following the reappearance of v-mos expression and v-mos kinase activity upon temperature shift, while the first manifestation of morphological transformation appears 24 h after the shift to permissive temperature. These results support the hypothesis that mos acts through the MKK to induce cell transformation.
我们已经在一个可诱导系统中，对响应v-mos癌基因温度敏感（ts）表达的MAP激酶级联反应的激活进行了表征。莫洛尼氏鼠肉瘤病毒（Mo-MuSVts110）的ts分离株对永生化大鼠胚胎成纤维细胞的转化，仅在允许温度下，当v-mos激酶存在且有活性时，才会组成性激活MAP激酶（ERK-1和ERK-2）以及MAP激酶激酶（MKK-1和MKK-2）。将ts转化的、血清饥饿的细胞从非允许温度转移到允许温度后，MAP激酶以及MKK-1和MKK-2在1-2小时内被激活，同时伴随着活性mos激酶的重新出现。Raf-1激酶活性对v-mos重新出现的反应增加得更慢，并且在温度转变18小时后才检测到表明过度磷酸化的迁移率变化。我们的数据表明，MAP激酶级联反应的激活是温度转变后v-mos表达和v-mos激酶活性重新出现后的早期事件，而形态转化的首次表现出现在转移到允许温度24小时后。这些结果支持了mos通过MKK诱导细胞转化的假说。
