The Interaction of Amphiregulin with Nuclei and Putative Nuclear Localization Sequence Binding Proteins

被引：38

作者：

Modrell, Brett ^{[1
]}

McDonald, Vicki L. ^{[1
]}

Shoyab, Mohammed ^{[1
]}

机构：

[1] Bristol Myers Squibb, Phurmuceut Res Inst, 3005 First Ave, Seattle, WA 98121 USA

来源：

GROWTH FACTORS | 1992年 / 7卷 / 04期

关键词：

amphiregulin; nuclear locator sequence binding proteins; growth regulators; DNA binding proteins;

D O I：

10.3109/08977199209046413

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Amphiregulin (AR) is a 23 kDa, bifunctional growth modulating glycoprotein belonging to the epidermal growth factor (EGF) family of polypeptide growth regulators. AR possesses two putative nuclear localization sequences (NLS), binds to DNA sepharose, and localizes to the nucleoli of human ovarian surface epithelial carcinoma cells suggesting that AR has a direct nuclear role. We have found that I-125-labeled AR, when exogenously applied to several carcinoma cell lines, associated with nuclei in a time, temperature, and concentration dependent fashion. The control peptide, EGF, also associated with these fractions but at approximately 20% of the effiiciency of AR. Cross-linking experiments with I-125-labeledAR and nuclear fractions derived from various carcinoma and normal cell lines demonstrated that AR binds two proteins of molecular mass 205 and 120 kDa. AR binding to these nuclear fraction proteins was specific and saturable as shown by competition experiments utilizing both SV-40 large T antigen NLS and an AR derived peptide encompassing both putative AR NLS. The combined results suggest that nuclear interactions may play a significant role in AR induced growth responses.

引用

页码：305 / 314

页数：10

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