Qui M S, Green S H
Department of Biology, University of Iowa, Iowa City 52242.
Neuron. 1992 Oct;9(4):705-17. doi: 10.1016/0896-6273(92)90033-a.
Expression of oncogenic ras in PC12 cells causes neuronal differentiation and sustained protein tyrosine phosphorylation and activity of extracellular signal-regulated kinases (ERKs), p42erk2 and p44erk1. Oncogenic N-ras-induced neuronal differentiation is inhibited by compounds that block ERK protein tyrosine phosphorylation or ERK activity, indicating that ERKs are not only activated by p21ras but serve as the primary downstream effectors of p21ras. Treatment of PC12 cells with nerve growth factor or fibroblast growth factor results in neuronal differentiation and in a sustained elevation of p21ras activity, of ERK activity, and of ERK tyrosine phosphorylation. Epidermal growth factor, which does not cause neuronal differentiation, stimulates only transient (< 1 hr) activation of p21ras and ERKs. These data indicate that transient activation of p21ras and, consequently, ERKs is not sufficient for induction of neuronal differentiation. Prolonged ERK activity is required: a consequence of sustained activation of p21ras by the growth factor receptor protein tyrosine kinase.
致癌性Ras在PC12细胞中的表达可导致神经元分化以及细胞外信号调节激酶（ERK）、p42erk2和p44erk1的持续蛋白酪氨酸磷酸化和活性。致癌性N-Ras诱导的神经元分化受到阻断ERK蛋白酪氨酸磷酸化或ERK活性的化合物的抑制，这表明ERK不仅被p21ras激活，而且是p21ras的主要下游效应器。用神经生长因子或成纤维细胞生长因子处理PC12细胞会导致神经元分化，并使p21ras活性、ERK活性和ERK酪氨酸磷酸化持续升高。不引起神经元分化的表皮生长因子仅刺激p21ras和ERK的短暂（<1小时）激活。这些数据表明，p21ras以及ERK的短暂激活不足以诱导神经元分化。需要延长ERK活性：这是生长因子受体蛋白酪氨酸激酶持续激活p21ras的结果。
