Cailliau K, Browaeys-Poly E, Vilain J P
Université des Sciences et Technologies de Lille, Laboratoire de Biologie du Développement, UE 1033, Bâtiment SN3, 59655 Cedex, Villeneuve D'Ascq, France.
Biochim Biophys Acta. 2001 Apr 23;1538(2-3):228-33. doi: 10.1016/s0167-4889(01)00074-x.
The mitogen-activated protein kinase (MAP kinase) signalling cascade activated by fibroblast growth factors (FGF1 and FGF2) was analysed in a model system, Xenopus oocytes, expressing fibroblast growth factor receptors (FGFR1 and FGFR4). Stimulation of FGFR1 by FGF1 or FGF2 and FGFR4 by FGF1 induced a sustained phosphorylation of extracellular signal-regulated protein kinase 2 (ERK2) and meiosis reinitiation. In contrast, FGFR4 stimulation by FGF2 induced an early transient activation of ERK2 and no meiosis reinitiation. FGFR4 transduction cascades were differently activated by FGF1 and FGF2. Early phosphorylation of ERK2 was blocked by the dominant negative form of growth factor-bound protein 2 (Grb2) and Ras, for FGF1-FGFR4 and FGF2-FGFR4. The phosphatidylinositol 3-kinase (PI3 kinase) inhibitors wortmannin and LY294002 only prevented the early ERK2 phosphorylation triggered by FGF2-FGFR4 but not by FGF1-FGFR4. ERK2 phosphorylation triggered by FGFR4 depended on the Grb2/Ras pathway and also involved PI3 kinase in a time-dependent manner.
在表达成纤维细胞生长因子受体（FGFR1和FGFR4）的非洲爪蟾卵母细胞这一模型系统中，对由成纤维细胞生长因子（FGF1和FGF2）激活的丝裂原活化蛋白激酶（MAP激酶）信号级联进行了分析。FGF1对FGFR1的刺激以及FGF1对FGFR4的刺激会诱导细胞外信号调节蛋白激酶2（ERK2）的持续磷酸化以及减数分裂重新启动。相比之下，FGF2对FGFR4的刺激会诱导ERK2的早期短暂激活，且不会引发减数分裂重新启动。FGF1和FGF2对FGFR4转导级联的激活方式不同。对于FGF1 - FGFR4和FGF2 - FGFR4，ERK2的早期磷酸化被生长因子结合蛋白2（Grb2）和Ras的显性负性形式所阻断。磷脂酰肌醇3激酶（PI3激酶）抑制剂渥曼青霉素和LY294002仅能阻止由FGF2 - FGFR4触发的ERK2早期磷酸化，而不能阻止由FGF1 - FGFR4触发的ERK2早期磷酸化。由FGFR4触发的ERK2磷酸化依赖于Grb2/Ras途径，并且还以时间依赖的方式涉及PI3激酶。
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