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Neu Differentiation Factor Stimulates Phosphorylation and Activation of the Sp1 Transcription Factor

机译:Neu分化因子刺激Sp1转录因子的磷酸化和激活。

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Neu differentiation factors (NDFs), or neuregulins, are epidermal growth factor-like growth factors which bind to two tyrosine kinase receptors, ErbB-3 and ErbB-4. The transcription of several genes is regulated by neuregulins, including genes encoding specific subunits of the acetylcholine receptor at the neuromuscular junction. Here, we have examined the promoter of the acetylcholine receptor ? subunit and delineated a minimal CA-rich sequence which mediates transcriptional activation by NDF (NDF-response element [NRE]). Using gel mobility shift analysis with an NRE oligonucleotide, we detected two complexes that are induced by treatment with neuregulin and other growth factors and identified Sp1, a constitutively expressed zinc finger phosphoprotein, as a component of one of these complexes. Phosphatase treatment, two-dimensional gel electrophoresis, and an in-gel kinase assay indicated that Sp1 is phosphorylated by a 60-kDa kinase in response to NDF-induced signals. Moreover, Sp1 seems to act downstream of all members of the ErbB family and thus may funnel the signaling of the ErbB network into the nucleus.
机译:神经分化因子(NDF)或神经调节蛋白是与两种酪氨酸激酶受体ErbB-3和ErbB-4结合的表皮生长因子样生长因子。几种基因的转录受神经调节蛋白调节,包括在神经肌肉接头处编码乙酰胆碱受体特定亚基的基因。在这里,我们研究了乙酰胆碱受体β的启动子。亚基并描绘了最小的富含CA的序列,该序列介导了NDF(NDF响应元件[NRE])的转录激活。使用NRE寡核苷酸进行的凝胶迁移率迁移分析,我们检测到了两种用神经调节蛋白和其他生长因子治疗诱导的复合物,并确定了Sp1(组成型表达的锌指磷蛋白)是其中一种复合物的组成部分。磷酸酶处理,二维凝胶电泳和凝胶内激酶测定表明,响应NDF诱导的信号,Sp1被60 kDa激酶磷酸化。此外,Sp1似乎在ErbB家族所有成员的下游起作用,因此可能会将ErbB网络的信号传导到核中。

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