Browaeys-Poly Edith, Broutin Isabelle, Antoine Anne-Frédérique, Marin Matthieu, Lescuyer Arlette, Vilain Jean Pierre, Ducruix Arnaud, Cailliau Katia
Laboratoire de Régulation des Signaux de Division, EA 4020, IFR 147, Bât. SN3, Université des Sciences et Technologies de Lille, 59655 Villeneuve d'Ascq Cedex, France.
Cell Signal. 2007 Dec;19(12):2540-8. doi: 10.1016/j.cellsig.2007.08.002. Epub 2007 Aug 15.
The injection of the Grb2 adapter in Xenopus oocytes promotes G2/M transition without stimulation from a receptor only the first day after the oocytes removal from the ovaries. This cell cycle reinitiation is Ras-dependent and requires the SH2 and SH3 domains of Grb2. The SH2 domain of Grb2 binds the tyrosine phosphorylated lipovitellin1, a homologue of the human apolipoprotein B. The N-SH3 domain of Grb2 is linked to a proline-rich sequence of the C2 domain of PLC-gamma1, PLC-gamma1 itself is linked, through its SH3 domain, to the C-terminal proline-rich region of Sos. When Grb2-PLC-gamma1-Sos is associated, PLC-gamma1 is not phosphorylated on Y783 but shows a phospholipase activity. Inhibition of lipovitellin 1 or PLC-gamma1 avoids Grb2-induced cell cycle reinitiation. Therefore, the Grb2-lipovitellin 1 association is the starting point of a novel signaling pathway, where PLC-gamma1 binds Grb2 and recruits Sos.
在非洲爪蟾卵母细胞中注射Grb2衔接蛋白，仅在卵母细胞从卵巢取出后的第一天，无需受体刺激就能促进G2/M期转换。这种细胞周期重新启动依赖于Ras，且需要Grb2的SH2和SH3结构域。Grb2的SH2结构域结合酪氨酸磷酸化的卵黄脂磷蛋白1，它是人类载脂蛋白B的同源物。Grb2的N-SH3结构域与磷脂酶C-γ1（PLC-γ1）C2结构域富含脯氨酸的序列相连，而PLC-γ1本身通过其SH3结构域与Sos的C端富含脯氨酸区域相连。当Grb2-PLC-γ1-Sos结合时，PLC-γ1在Y783位点未被磷酸化，但具有磷脂酶活性。抑制卵黄脂磷蛋白1或PLC-γ1可避免Grb2诱导的细胞周期重新启动。因此，Grb2与卵黄脂磷蛋白1的结合是一条新信号通路的起点，在该通路中，PLC-γ1结合Grb2并招募Sos。
