Prolonged ERK activation events

After NGF binding, activated Trk receptors provide multiple docking sites for adaptor proteins and enzymes. Two docking proteins, the Ankyrin-Rich Membrane Spanning protein (ARMS/Kidins220) and Fibroblast growth factor receptor substrate 2 (Frs2), target signaling molecules in response to NGF stimulation and link receptor activation with the MAP kinase (also called the Extracellular signal-Regulated Kinase cascade, ERK) cascade, an essential process for growth factor-induced cell proliferation and differentiation.<br>A feature of NGF signaling is the sustained activation of the MAPK cascade. This is achieved by the small G protein, Rap1 which binds to and activates B-Raf, an activator of the MAPK cascade. Rap1 is a member of the Ras family of G proteins and like all G proteins, Rap1 is in an inactive state when bound to GDP and is active when bound to GTP. A specific GEF (guanine nucleotide exchange factor) called C3G can activate Rap1 by exchanging GDP for GTP.

在神经营养因子（NGF）结合之后，激活的Trk受体为适配蛋白和酶提供了多个结合位点。两种结合蛋白，即富含ankyrin的跨膜蛋白（ARMS/Kidins220）和成纤维细胞生长因子受体底物2（Frs2），在NGF刺激下针对信号分子进行靶向，并将受体激活与丝裂原活化蛋白激酶（简称MAP激酶，亦称细胞外信号调节激酶级联反应，ERK级联反应）联系起来，这一级联反应对于生长因子诱导的细胞增殖和分化至关重要。NGF信号传导的特征是MAPK级联反应的持续激活。这一过程通过小G蛋白Rap1实现，Rap1与B-Raf结合并激活MAPK级联反应。Rap1是Ras家族G蛋白的一员，与所有G蛋白一样，Rap1在GDP结合时处于非活性状态，而在GTP结合时处于活性状态。一种特定的鸟苷酸交换因子（GEF）C3G可以通过交换GDP与GTP来激活Rap1。