c-erbB-3: a nuclear protein in mammary epithelial cells.
c-erbB-3: a nuclear protein in mammary epithelial cells.
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DOI：
10.1083/jcb.200109033
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发表时间：
2002-06-10
期刊：
影响因子：
--
通讯作者：
Grunt TW
中科院分区：
文献类型：
--
作者：
Offterdinger M;Schöfer C;Weipoltshammer K;Grunt TW
c-erbB受体通常位于细胞膜上，并通过EGF样生长因子的细胞外结合而激活。出乎意料的是，使用免疫荧光，我们发现高水平的c-erbB-3的MTSV 1 -7永生化的非恶性人类乳腺上皮细胞的细胞核内。通过c-erbB-3的COOH末端介导核定位，并且通过定点诱变和通过将信号转移到鸡丙酮酸激酶来鉴定核定位信号。一个核输出抑制剂引起的其他乳腺上皮细胞系的细胞核中的c-erbB-3的积累所证明的免疫荧光和生化细胞分级，这表明c-erbB-3穿梭在这些细胞的核和非核隔间。MTSV 1 -7在可渗透过滤器上的生长诱导上皮极性和核仁内c-erbB-3的浓度。而c-erbB-3配体heregulin β1使c-erbB-3从核仁进入核质，然后进入胞质。c-erbB-3的亚细胞定位显然取决于外源性刺激和上皮极性的阶段，并挑战c-erbB-3作为跨膜受体蛋白的特异性功能，从而论证了c-erbB-3在乳腺上皮细胞核内的额外的、尚未鉴定的作用。
c-erbB receptors are usually located in cell membranes and are activated by extracellular binding of EGF-like growth factors. Unexpectedly, using immunofluorescence we found high levels of c-erbB-3 within the nuclei of MTSV1-7 immortalized nonmalignant human mammary epithelial cells. Nuclear localization was mediated by the COOH terminus of c-erbB-3, and a nuclear localization signal was identified by site-directed mutagenesis and by transfer of the signal to chicken pyruvate kinase. A nuclear export inhibitor caused accumulation of c-erbB-3 in the nuclei of other mammary epithelial cell lines as demonstrated by immunofluorescence and biochemical cell fractionation, suggesting that c-erbB-3 shuttles between nuclear and nonnuclear compartments in these cells. Growth of MTSV1-7 on permeable filters induced epithelial polarity and concentration of c-erbB-3 within the nucleoli. However, the c-erbB-3 ligand heregulin β1 shifted c-erbB-3 from the nucleolus into the nucleoplasm and then into the cytoplasm. The subcellular localization of c-erbB-3 obviously depends on exogenous stimuli and on the stage of epithelial polarity and challenges the specific function of c-erbB-3 as a transmembrane receptor protein arguing for additional, as yet unidentified, roles of c-erbB-3 within the nucle(ol)us of mammary epithelial cells.
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影响因子：
21.3
作者：
Lin, SY;Makino, K;Hung, MC
通讯作者：
Hung, MC
DOI：
10.1073/pnas.91.17.8132
发表时间：
1994-08-16
影响因子：
11.1
作者：
GUY, PM;PLATKO, JV;CARRAWAY, KL
通讯作者：
CARRAWAY, KL
影响因子：
14.9
作者：
Reinhardt, A;Hubbard, T
通讯作者：
Hubbard, T
影响因子：
8.8
作者：
RAJKUMAR, T;GULLICK, WJ
通讯作者：
GULLICK, WJ
DOI：
10.1073/pnas.96.16.9112
发表时间：
1999-08-03
影响因子：
11.1
作者：
Kudo, N;Matsumori, N;Horinouchi, S
通讯作者：
Horinouchi, S