Aggregation of IGF-I receptors or insulin receptors and activation of their kinase activity are simultaneously caused by the presence of polycations or K-ras basic peptides.
Aggregation of IGF-I receptors or insulin receptors and activation of their kinase activity are simultaneously caused by the presence of polycations or K-ras basic peptides.
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IGF-I受体或胰岛素受体的聚集及其激酶活性的激活是由聚阳离子或K-ras碱性肽的存在同时引起的。
DOI：
10.1021/bi00115a011
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发表时间：
1991
期刊：
影响因子：
2.9
通讯作者：
Fujita-Yamaguchi,Y
中科院分区：
文献类型：
--
作者：
Xu,QY;Li,SL;LeBon,TR;Fujita-Yamaguchi,Y
修订后的手稿于 1991 年 9 月 13 日收到摘要：包括我们在内的几个小组报告称，碱性蛋白和聚阳离子在体外激活胰岛素受体酪氨酸特异性蛋白激酶 (TPK)。然而，观察结果中出现了一些明显的不一致之处。最有趣的是 Morrison 等人的简短描述。[(1989) J. Biol。化学。 264, 9994-10001] 尽管聚赖氨酸与胰岛素受体 TPK 有 84% 的同一性，但它对 IGF-I 受体 TPK 没有影响。在本研究中，我们使用高度纯化的 IGF-I 和胰岛素受体 TPK，试图解决最近出版物中指出的差异，并揭示聚阳离子刺激受体 TPK 的机制。我们报告说，IGF-I 受体 TPK 受到聚阳离子和碱性蛋白的刺激，其方式类似于它们对胰岛素受体 TPK 的影响。当仔细比较聚赖氨酸和聚精氨酸对两种受体TPK的影响时，发现了细微的质的差异：聚赖氨酸类似地刺激胰岛素受体TPK和IGF-I受体TPK的自身磷酸化和外源底物磷酸化活性。相比之下，另一种聚阳离子聚精氨酸以与聚赖氨酸完全不同的方式影响两种TPK：聚精氨酸比聚赖氨酸更大程度地刺激胰岛素受体自身磷酸化，而它对IGF-I受体自身磷酸化以及两种受体TPK的外源底物磷酸化活性的影响非常小。我们进一步扩展了研究范围，将含有多聚赖氨酸样序列的天然蛋白质领域纳入其中。这种肽，即 K-ras 肽，对两种受体 TPK 具有与聚阳离子类似的作用。最后，通过非变性梯度聚丙烯酰胺凝胶电泳和蔗糖密度梯度离心判断，我们观察到聚阳离子和K-ras肽引起受体聚集。这些研究表明受体聚集与 IGF-I 和胰岛素受体 TPK 的激活之间存在很强的相关性，这可能是由 K-ras 产物等细胞蛋白引起的。
Revised Manuscript Received September 13, 1991 abstract: Several groups including us reported that basic proteins and polycations activate the insulin receptor tyrosine-specific protein kinase (TPK) in vitro. However, some inconsistency has become obvious in theobservations. The most intriguing was the brief description by Morrison et al.[(1989) J. Biol. Chem. 264, 9994-10001] that polylysine had no effect on the IGF-I receptor TPK despite its 84% identity to the insulin receptor TPK. In the present study, we used highly purified IGF-I and insulin receptor TPKs in an effort to solve the discrepancies noted in the recent publications and to reveal the mechanism by which polycations stimulate the receptor TPKs. We report that the IGF-I receptor TPK is stimulated by polycations and basic proteins in a manner similar to their effects on the insulin receptor TPK. When effects of polylysine and polyarginine on both receptor TPKs were closely compared, subtle qualitative differences were found: Polylysine stimulated autophosphorylation and exogenous substratephosphorylation activities of both insulin receptor TPK and IGF-I receptor TPK similarly. In contrast, another polycation, polyarginine, affected both TPKs in a manner quite different from polylysine: Polyarginine stimulated insulin receptor autophosphorylation to a greater extent than polylysine did while it had a very small effect on the IGF-I receptor autophosphorylation as well as the exogenous substrate phosphorylation activities of the two receptor TPKs. We have further extended the studies to include the domains of natural proteins which contain a polylysine-like sequence. Such peptides, K-ras peptides, had similar effects on the two receptor TPKs to those of polycations. Finally, we observed that polycations and K-ras peptides caused receptor aggregation as judged by nondenaturing gradient polyacrylamide gel electrophoresis and sucrose density gradient centrifugation. These studies suggest a strong correlation between receptor aggregation and activation of IGF-I and insulin receptor TPKs which may be caused by cellular proteins such as K-ras products.