Mutational analysis of the mitogenic and transforming activities of the insulin-like growth factor I receptor.

Mutational analysis of the mitogenic and transforming activities of the insulin-like growth factor I receptor.
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胰岛素样生长因子 I 受体促有丝分裂和转化活性的突变分析。

DOI:
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发表时间:
1996
期刊:
影响因子:
8
通讯作者:
R. Baserga
R. Baserga
中科院分区:
医学1区
文献类型:
--
作者:
A. Hongo;C. D’Ambrosio;M. Miura;A. Morrione;R. Baserga

文献摘要

被引文献

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I型胰岛素样生长因子受体(IGF-IR)在细胞有丝分裂和转化过程中起重要作用。以前的研究表明,IGF-IR的促有丝分裂信号和转化活性是可以分离的:1229位残基(C-末端)截短的受体对IGF-I的反应是完全有丝分裂的,但不能转化缺乏内源性IGF-IR的3T3样细胞(R细胞)。我们通过稳定地将几个突变的受体导入R细胞,并测试得到的细胞系的IGF-I介导的有丝分裂反应和软琼脂中克隆的形成,扩展了我们对人IGF-IR的C末端的突变分析。结果表明,IGF-IR的转化域可以定位在残基1245和1310之间,这些序列不是有丝分裂信号所必需的。在这些残基中,至少有两个区域有助于受体的转化活性。
THe type 1 insulin-like growth factor receptor (IGF-IR) plays an important role in mitogenesis and transformation. It has been previously shown that mitogenic signaling and transforming activity of the IGF-IR can be dissociated: a receptor truncated at residue 1229 (C-terminus) is fully mitogenic, in terms of its response to IGF-I, but cannot transform 3T3-like cells that are devoid of endogenous IGF-IRs (R- cells). We have extended our mutational analysis of the C-terminus of the human IGF-IR, by stably transfecting several mutant receptors into R- cells, and testing the resulting cell lines for IGF-I-mediated mitogenic response and formation of colonies in soft agar. The results indicate that the transforming domain of the IGF-IR can be localized between residues 1245 and 1310, these sequences being not required for mitogenic signaling. Within these residues, there are at least two areas that contribute to the transforming activity of the receptor.