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Induction of neurite outgrowth by v-src mimics critical aspects of nerve growth factor-induced differentiation.

机译:v-src诱导的神经突生长模拟神经生长因子诱导的分化的关键方面。

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PC12 cells treated with nerve growth factor (NGF) or infected with Rous sarcoma virus differentiate into sympathetic, neuronlike cells. To compare the differentiation programs induced by NGF and v-src, we have established a PC12 cell line expressing a temperature-sensitive v-src protein. The v-src-expressing PC12 cell line was shown to elaborate neuritic processes in a temperature-inducible manner, indicating that the differentiation process was dependent on the activity of the v-src protein. Further characterization of this cell line, in comparison with NGF-treated PC12 cells, indicated that the events associated with neurite outgrowth induced by these two agents shared features but could be distinguished by others. Both NGF- and v-src-induced neurite outgrowths were reversible. In addition, NGF and v-src could prime PC12 cells for NGF-induced neurite outgrowth, and representative early and late NGF-responsive genes were also induced by v-src. However, unlike NGF-induced neurite growth, v-src-induced neurite outgrowth was not blocked at high cell density. A comparison of phosphotyrosine containing-protein profiles showed that v-src and NGF each increase tyrosine phosphorylation of multiple cellular proteins. There was overlap in substrates; however, both NGF-specific and v-src-specific tyrosine phosphorylations were observed. One protein which was found to be phosphorylated in both the NGF- and v-src-induced PC12 cells was phospholipase C-gamma 1. Taken together, these results suggest that v-src's ability to function as an inducing agent may be a consequence of its ability to mimic critical aspects of the NGF differentiation program and raise the possibility that Src-like tyrosine kinases are involved in mediating some of the events triggered by NGF.
机译:用神经生长因子(NGF)处理或感染劳斯肉瘤病毒的PC12细胞分化为交感神经元样细胞。为了比较NGF和v-src诱导的分化程序,我们建立了表达温度敏感性v-src蛋白的PC12细胞系。已显示表达v-src的PC12细胞系以温度可诱导的方式完善了神经过程,表明分化过程取决于v-src蛋白的活性。与NGF处理的PC12细胞相比,该细胞系的进一步表征表明,与这两种药物诱导的神经突增生相关的事件具有共同的特征,但可以被其他特征区分开。 NGF和v-src诱导的神经突增生都是可逆的。此外,NGF和v-src可以引发PC12细胞发生NGF诱导的神经突生长,v-src也可以诱导代表性的早期和晚期NGF应答基因。但是,与NGF诱导的神经突生长不同,v-src诱导的神经突向外生长在高细胞密度下没有被阻止。含磷酸酪氨酸的蛋白谱的比较表明,v-src和NGF各自增加了多种细胞蛋白的酪氨酸磷酸化。基材重叠。然而,NGF特异性和v-src特异性酪氨酸磷酸化均被观察到。 NGF和v-src诱导的PC12细胞均被磷酸化的一种蛋白是磷脂酶C-γ1。这些结果加在一起,这些结果表明v-src发挥诱导剂的能力可能是由于以下原因导致的:它具有模仿NGF分化程序关键方面的能力,并提高了Src样酪氨酸激酶参与介导NGF触发的某些事件的可能性。

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