MacNicol A M, Muslin A J, Howard E L, Kikuchi A, MacNicol M C, Williams L T
Daiichi Research Center, Cardiovascular Research Institute, University of California at San Francisco 94143, USA.
Mol Cell Biol. 1995 Dec;15(12):6686-93. doi: 10.1128/MCB.15.12.6686.
The Raf-1 gene product is activated in response to cellular stimulation by a variety of growth factors and hormones. Raf-1 activity has been implicated in both cellular differentiation and proliferation. We have examined the regulation of the Raf-1/MEK/MAP kinase (MAPK) pathway during embryonic development in the frog Xenopus laevis. We report that Raf-1, MEK, and MAPK activities are turned off following fertilization and remain undetectable up until blastula stages (stage 8), some 4 h later. Tight regulation of the Raf-1/MEK/MAPK pathway following fertilization is crucial for embryonic cell cycle progression. Inappropriate reactivation of MAPK activity by microinjection of oncogenic Raf-1 RNA results in metaphase cell cycle arrest and, consequently, embryonic lethality. Our findings demonstrate an absolute requirement, in vivo, for inactivation of the MAPK signaling pathway to allow normal cell cycle progression during the period of synchronous cell divisions which occur following fertilization. Further, we show that cytostatic factor effects are mediated through MEK and MAPK.
Raf-1基因产物可响应多种生长因子和激素的细胞刺激而被激活。Raf-1活性与细胞分化和增殖均有关联。我们研究了非洲爪蟾胚胎发育过程中Raf-1/MEK/丝裂原活化蛋白激酶（MAPK）信号通路的调控。我们发现，受精后Raf-1、MEK和MAPK活性会关闭，直至囊胚期（第8期）约4小时后仍检测不到。受精后对Raf-1/MEK/MAPK信号通路的严格调控对胚胎细胞周期进程至关重要。通过显微注射致癌性Raf-1 RNA不当重新激活MAPK活性会导致中期细胞周期停滞，进而导致胚胎致死。我们的研究结果表明，在体内，MAPK信号通路失活是受精后同步细胞分裂期间正常细胞周期进程的绝对必要条件。此外，我们还表明，细胞静止因子的作用是通过MEK和MAPK介导的。
