The functions for Ras/Ral signaling cascade

RAS蛋白具有影响多种细胞过程的能力，包括细胞周期控制、诱导分化、肌动蛋白重排和细胞凋亡。我们确定了RalBP1的另一个潜在结合伙伴。该蛋白具有EPS同源(EH)结构域，并在EGF信号转导下被酪氨酸磷酸化。RalBP1相关的EPS结构域包含蛋白(Rep)可能介导了RalBP1的一项附加功能。此外，Rep具有与适配蛋白Crk和Grb2的SH3结构域形成复合体的能力，这可能将Rep与EGF反应的酪氨酸激酶联系起来。REPS可以协调激活的EGF受体和Ral-GTP酶的细胞作用。我们研究了Ral-GTP信号通路在NGF诱导PC12细胞分化中的作用。与Raf和PI3激酶信号相反的是Ral-gef信号通路。结果表明，RAS活性的结构性升高抑制了NGF诱导的神经突起生长和细胞周期停滞，而RAR活性的结构性抑制则增加了NGF诱导的神经突起生长和细胞周期退出的比率，RAS效应分子之间的活性比率及其时间调控可能是决定细胞增殖和分化命运的重要决定因素。

Ras proteins have the capacity to influence a wide variety of cellular processes, including cell cycle control, induction of differentiation, rearrangement of the actin cytoskelton, and apoptosis. We identify another potential binding partner for RalBP1. This protein has an Eps homology (EH) domain and becomes tyrosine-phosphorylated in response to EGF signaling. RalBP1 associated Eps domain-containing protein (Reps) may mediate an additional function of RalBP1. In addition, Reps has the capacity to form a complex with the SH3 domains of the adapter proteins Crk and Grb2, which may link Reps to an EGF-responsive tyrosine kinase. Reps may coordinate the cellular actions of activated EGF receptors and Ral-GTPase.And we investigated the contribution of the Ral-GEF signaling pathway to NGF-induced differentiation of PC12cells. Ral-GEF signaling opposed the actions of Raf and PI3 kinase signaling. Constitutive elevation of Ral-GEF activity suppressed neurite outgrowth and cell cycle arrest induced by NGF, whereas constitutive inhibition of Ral-GEF activity enhanced the rate of NGF-induced neurite outgrowth and cell cycle exit.The ratio of activities among Ras effectors and their temporal regulation may be important determinants for cell fate decision between proliferation and differentiation.