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首页> 外文期刊>Molecular and Cellular Biology >Identification of domains of the insulin-like growth factor I receptor that are required for protection from apoptosis.
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Identification of domains of the insulin-like growth factor I receptor that are required for protection from apoptosis.

机译：鉴定胰岛素样生长因子I受体的保护细胞凋亡所需的域。

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Using a series of insulin-like growth factor I (IGF-I) receptor mutants, we have attempted to define domains required for transmitting the antiapoptotic signal from the receptor and to compare these domains with those required for mitogenesis or transformation. In FL5.12 cells transfected with wild-type IGF-I receptors, IGF-I affords protection from interleukin 3 withdrawal but is not mitogenic. An IGF-I receptor lacking a functional ATP binding site provided no protection from apoptosis. However, receptors mutated at tyrosine residue 950 or in the tyrosine cluster (1131, 1135, and 1136) within the kinase domain remained capable of suppressing apoptosis, although such mutations are known to inactivate transforming and mitogenic functions. In the C terminus of the IGF-I receptor, two mutations, one at tyrosine 1251 and one which replaced residues histidine 1293 and lysine 1294, abolished the antiapoptotic function, whereas mutation of the four serines at 1280 to 1283 did not. Interestingly, receptors truncated at the C terminus had enhanced antiapoptotic function. In Rat-1/ c-MycER fibroblasts, the Y950F mutant and the tyrosine cluster mutant could still provide protection from c-Myc-induced apoptosis, whereas mutant Y1250/1251F could not. These studies demonstrate that the domains of the IGF-I receptor required for its antiapoptotic function are distinct from those required for its proliferation or transformation functions and suggest that domains of the receptor required for inhibition of apoptosis are necessary but not sufficient for transformation.
机译：我们使用一系列胰岛素样生长因子I（IGF-I）受体突变体，试图定义从受体传递抗凋亡信号所需的结构域，并将这些结构域与促有丝分裂或转化所需的结构域进行比较。在用野生型IGF-I受体转染的FL5.12细胞中，IGF-I可以防止白介素3撤离，但不会促有丝分裂。缺少功能性ATP结合位点的IGF-I受体不能提供抗凋亡保护。但是，激酶结构域内酪氨酸残基950或酪氨酸簇（1131、1135和1136）中发生突变的受体仍然能够抑制细胞凋亡，尽管已知这种突变可以使转化和促有丝分裂功能失活。在IGF-I受体的C末端，两个突变，一个在酪氨酸1251突变，一个替换了组氨酸1293和赖氨酸1294残基，取消了抗凋亡功能，而四个丝氨酸在1280-1283突变。有趣的是，在C末端截短的受体具有增强的抗凋亡功能。在Rat-1 / c-MycER成纤维细胞中，Y950F突变体和酪氨酸簇突变体仍然可以保护c-Myc诱导的细胞凋亡，而突变体Y1250 / 1251F不能。这些研究表明，其抗凋亡功能所需的IGF-I受体的结构域与其增殖或转化功能所需的域不同，并且表明抑制细胞凋亡所需的受体的结构域对于转化是必需的，但不足。

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