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首页> 外文期刊>Molecular and Cellular Biology >Single-chain antibody-mediated intracellular retention of ErbB-2 impairs Neu differentiation factor and epidermal growth factor signaling.
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Single-chain antibody-mediated intracellular retention of ErbB-2 impairs Neu differentiation factor and epidermal growth factor signaling.

机译：单链抗体介导的ErbB-2的细胞内滞留会损害Neu分化因子和表皮生长因子信号传导。

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ErbB-2 becomes rapidly phosphorylated and activated following treatment of many cell lines with epidermal growth factor (EGF) or Neu differentiation factor (NDF). However, these factors do not directly bind ErbB-2, and its activation is likely to be mediated via transmodulation by other members of the type I/EGF receptor (EGFR)-related family of receptor tyrosine kinases. The precise role of ErbB-2 in the transduction of the signals elicited by EGF and NDF is unclear. We have used a novel approach to study the role of ErbB-2 in signaling through this family of receptors. An ErbB-2-specific single-chain antibody, designed to prevent transit through the endoplasmic reticulum and cell surface localization of ErbB-2, has been expressed in T47D mammary carcinoma cells, which express all four known members of the EGFR family. We show that cell surface expression of ErbB-2 was selectively suppressed in these cells and that the activation of the mitogen-activated protein kinase pathway and p70/p85S6K, induction of c-fos expression, and stimulation of growth by NDF were dramatically impaired. Activation of mitogen-activated protein kinase and p70/p85S6K and induction of c-fos expression by EGF were also significantly reduced. We conclude that in T47D cells, ErbB-2 is a major NDF signal transducer and a potentiator of the EGF signal. Thus, our observations demonstrate that ErbB-2 plays a central role in the type I/EGFR-related family of receptors and that receptor transmodulation represents a crucial step in growth factor signaling.
机译：用表皮生长因子（EGF）或Neu分化因子（NDF）处理许多细胞系后，ErbB-2迅速磷酸化并被激活。但是，这些因子并不直接结合ErbB-2，其激活可能是由I / EGF受体（EGFR）型酪氨酸激酶相关家族的其他成员通过转调介导的。 ErbB-2在EGF和NDF引发的信号转导中的确切作用尚不清楚。我们已经使用一种新颖的方法来研究ErbB-2在通过该受体家族进行信号传导中的作用。在T47D乳腺癌细胞中已经表达了一种ErbB-2特异性单链抗体，旨在防止其穿过内质网和ErbB-2的细胞表面定位，并表达EGFR家族的所有四个已知成员。我们表明，在这些细胞中，ErbB-2的细胞表面表达被选择性抑制，促分裂原活化的蛋白激酶途径和p70 / p85S6K的激活，c-fos表达的诱导以及NDF的生长刺激显着受损。 EGF对丝裂原活化蛋白激酶和p70 / p85S6K的激活以及c-fos表达的诱导也显着降低。我们得出结论，在T47D细胞中，ErbB-2是主要的NDF信号传感器和EGF信号的增强剂。因此，我们的观察结果表明，ErbB-2在I / EGFR相关受体家族中起着核心作用，并且受体转调代表了生长因子信号传导中的关键步骤。

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