Ras mediates Src but not epidermal growth factor-receptor tyrosine kinase signaling pathways in GH4 neuroendocrine cells.
Ras mediates Src but not epidermal growth factor-receptor tyrosine kinase signaling pathways in GH4 neuroendocrine cells.
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Ras 介导 GH4 神经内分泌细胞中的 Src，但不介导表皮生长因子受体酪氨酸激酶信号通路。
DOI：
10.1073/pnas.91.18.8612
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发表时间：
1994
影响因子：
11.1
通讯作者：
Gutierrez-Hartmann,A
中科院分区：
文献类型：
--
作者：
Pickett,CA;Gutierrez-Hartmann,A
p21 Ras是介导许多生长因子受体/酪氨酸激酶对细胞生长和分化的作用的关键信号组分。然而，Ras在建立对普遍存在的生长因子的细胞特异性转录反应中的确切功能作用仍不清楚。我们利用瞬时共转染模型系统在表皮生长因子（EGF）响应培养的GH4大鼠垂体神经内分泌细胞中研究Ras在偶联EGF受体（EGF-R）和v-Src酪氨酸激酶信号激活大鼠催乳素（PRL）基因的细胞特异性启动子中的作用。一个显着的剂量和时间依赖性EGF刺激的转染rPRL启动子。通过共转染编码v-Src的质粒获得了类似程度的rPRL启动子的激活。共转染的构建体编码的显性负Ras，N17 Ras，产生几乎完全抑制v-Src诱导的rPRL启动子活性，而EGF刺激的rPRL启动子活性不受影响。类似地，EGF对c-Fos启动子的激活不受N17 Ras的影响，而v-Src的激活被阻断。因此，使用转录调控作为一个功能性的测定，我们表明，Ras是不需要的EGF介导的控制的rPRL和c-Fos启动子，而Ras是至关重要的介导的v-Src的影响，这两个启动子。这些观察结果强调，尽管目前的生物化学数据连接EGF-R和Ras途径，这种相互作用的功能意义应在生物学相关的方式进行分析，并可能不同的细胞类型的功能。
p21Ras has been implicated as a critical signaling component in mediating the effects of many growth factor receptor/tyrosine kinases on cell growth and differentiation. However, the precise functional role of Ras in establishing a cell-specific transcriptional response to a ubiquitous growth factor remains unclear. We have utilized a transient cotransfection model system in epidermal growth factor (EGF)-responsive cultured GH4 rat pituitary neuroendocrine cells to investigate the role of Ras in coupling EGF receptor (EGF-R) and v-Src tyrosine kinase signals to the activation of a cell-specific promoter for the rat (r) prolactin (PRL) gene. A significant dose- and time-dependent EGF stimulation of the transfected rPRL promoter was obtained. A similar degree of activation of the rPRL promoter was obtained by cotransfection of a plasmid encoding v-Src. Cotransfection of a construct encoding the dominant-negative Ras, N17Ras, produced almost complete inhibition of v-Src-induced rPRL promoter activity, while EGF-stimulated rPRL promoter activity was unaffected. Similarly, EGF activation of a c-Fos promoter was unaffected by N17Ras, while v-Src activation was blocked. Hence, using transcription regulation as a functional assay, we show that Ras is not required for the EGF-mediated control of the rPRL and c-Fos promoters, whereas Ras is critical in mediating the v-Src effects to these two promoters. These observations emphasize that, despite current biochemical data linking the EGF-R and Ras pathways, the functional significance of such an interaction should be analyzed in a biologically relevant manner and may differ as a function of cell type.
影响因子：
64.8
作者：
MURDOCH, GH;POTTER, E;ROSENFELD, MG
通讯作者：
ROSENFELD, MG
调节垂体细胞特异性基因表达的 Ras 信号通路功能成分的鉴定
影响因子：
5.3
作者：
Kerry E. Conrad;J. M. Oberwetter;R. Vaillancourt;Gary L. Johnson;A. Gutierrez
通讯作者：
A. Gutierrez