Identification of nucleolin as new ErbB receptors- interacting protein.
Identification of nucleolin as new ErbB receptors- interacting protein.
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DOI：
10.1371/journal.pone.0002310
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发表时间：
2008-06-04
期刊：
影响因子：
3.7
通讯作者：
Pinkas-Kramarski, Ronit
中科院分区：
文献类型：
--
作者：
Di Segni, Ayelet;Farin, Keren;Pinkas-Kramarski, Ronit
ErbB受体酪氨酸激酶是恶性转化的主要贡献者。这些受体经常在各种人类癌症中过度表达。ErbB受体及其配体在癌症中的作用及其过度表达导致癌症发生的机制尚不清楚。与特定ErbB受体的配体结合后，受体二聚化、磷酸化和募集含有SH2的细胞质蛋白，启动了一系列信号事件。然而，越来越多的数据表明，存在非磷酸化的受体-底物相互作用，可能会影响ErbB介导的反应。在本研究中，我们利用GST-ErbB4融合蛋白下拉实验和质谱分析，发现ErbB受体通过细胞质尾巴与核仁相互作用。核仁是一种普遍存在的、非组蛋白、核仁、多功能的磷酸蛋白，在癌细胞中也有过表达。我们的结果表明，ErbB1和核仁过表达可能导致受体二聚化、磷酸化和锚定非依赖性生长。ErbB的致癌潜能取决于受体水平和激活程度。我们的结果表明，核仁素可能影响ErbB的二聚化和激活，从而促进细胞生长。
The ErbB receptor tyrosine kinases are major contributors to malignant transformation. These receptors are frequently overexpressed in a variety of human carcinomas. The role of the ErbB receptors and their ligands in carcinomas and the mechanism by which their overexpression leads to cancer development is still unclear. Ligand binding to specific ErbB receptor is followed by receptor dimerization, phosphorylation and recruitment of SH2 containing cytoplasmic proteins, which initiate the cascade of signaling events. Nevertheless, increasing data suggest that there are non-phosphorylated receptor–substrate interactions that may affect ErbB-mediated responses. In the present study, using GST-ErbB4 fusion protein pull down assay and mass spectroscopic analysis, we have found the ErbB receptors interact with nucleolin via their cytoplasmic tail. Nucleolin is a ubiquitous, nonhistone, nucleolar, multifunctional phosphoprotein that is also overexpressed in cancer cells. Our results demonstrate that overexpression of ErbB1 and nucleolin may lead to receptor dimerization, phosphorylation and to anchorage independent growth. The oncogenic potential of ErbB depends on receptor levels and activation. Our results suggest that nucleolin may affect ErbB dimerization and activation leading to enhanced cell growth.
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DOI：
10.1111/j.1742-4658.2006.05471.x
发表时间：
2006-10
期刊：
The FEBS journal
影响因子：
--
作者：
Alete DE;Weeks ME;Hovanession AG;Hawadle M;Stoker AW
通讯作者：
Stoker AW
影响因子：
21.3
作者：
Lin, SY;Makino, K;Hung, MC
通讯作者：
Hung, MC
影响因子：
56.9
作者：
COUSSENS, L;YANGFENG, TL;ULLRICH, A
通讯作者：
ULLRICH, A
影响因子：
3.7
作者：
FANG, SH;YEH, NH
通讯作者：
YEH, NH
DOI：
10.1073/pnas.84.6.1472
发表时间：
1987-03-01
影响因子：
11.1
作者：
LAPEYRE, B;BOURBON, H;AMALRIC, F
通讯作者：
AMALRIC, F