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抗受体抗体作为胰岛素样生长因子受体结构的探针。

Antireceptor antibodies as probes of insulinlike growth factor receptor structure.

作者信息

Kasuga M, Sasaki N, Kahn C R, Nissley S P, Rechler M M

出版信息

J Clin Invest. 1983 Oct;72(4):1459-69. doi: 10.1172/JCI111102.

DOI:10.1172/JCI111102
PMID:6313762
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC370430/
Abstract

Insulin receptors and Type I insulinlike growth factor (IGF) receptors have a similar structure with a major binding subunit of Mr approximately 130,000 linked by disulfide bonds to other membrane proteins to form a Mr greater than 300,000 complex. Both insulin and Type I IGF receptors also interact with both insulin and IGF, although with different binding affinities. We used a panel of human and rabbit sera containing antibodies to insulin receptors to determine whether these sera also interact with Type I IGF receptors. Immunoglobulins from five of five human sera inhibited binding of 125I-insulin and 125I-IGF-I to insulin receptors and Type I IGF receptors in human placenta and human lymphocytes. The rank order of reactivity with both receptors was the same; two sera, however, appeared to be selectively less reactive with the Type I IGF receptor, especially in placenta. Sera from five of seven patients and from a rabbit immunized with purified insulin receptor effectively immunoprecipitated both placental insulin receptors and Type I IGF receptors. Of the remaining sera, one had only a low titer against the insulin receptor and did not immunoprecipitate the IGF receptor, whereas the second serum effectively immunoprecipitated cross-linked and surface-iodinated insulin receptors, but had negligible reactivity against the Type I IGF receptor. These results suggest that most antisera to the insulin receptor also contain antibodies to Type I IGF receptors. Whether both specificities are inherent in the same or different antibody molecules remains to be determined. These data support the hypothesis that the insulin and IGF-I receptors are separate but related molecules, although there remains a small possibility that both receptors are domains on the same protein.

摘要

胰岛素受体和I型胰岛素样生长因子(IGF)受体具有相似的结构,其主要结合亚基的分子量约为130,000,通过二硫键与其他膜蛋白相连,形成分子量大于300,000的复合物。胰岛素和I型IGF受体均能与胰岛素和IGF相互作用,不过结合亲和力有所不同。我们使用了一组含有胰岛素受体抗体的人血清和兔血清,以确定这些血清是否也能与I型IGF受体相互作用。五份人血清中的免疫球蛋白均抑制了125I-胰岛素和125I-IGF-I与人胎盘和人淋巴细胞中胰岛素受体及I型IGF受体的结合。与两种受体反应性的排序相同;然而,有两份血清与I型IGF受体的反应性似乎选择性降低,尤其是在胎盘中。七名患者中的五名患者的血清以及用纯化胰岛素受体免疫的兔血清有效地免疫沉淀了胎盘胰岛素受体和I型IGF受体。其余血清中,一份对胰岛素受体的滴度较低,未免疫沉淀IGF受体,而另一份血清有效地免疫沉淀了交联和表面碘化的胰岛素受体,但对I型IGF受体的反应性可忽略不计。这些结果表明,大多数针对胰岛素受体的抗血清也含有针对I型IGF受体的抗体。两种特异性是存在于相同还是不同的抗体分子中仍有待确定。这些数据支持了胰岛素和IGF-I受体是独立但相关分子的假说,尽管仍有很小的可能性两种受体是同一蛋白质上的结构域。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5125/370430/a8c149bb9ccb/jcinvest00708-0287-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5125/370430/22432e54da17/jcinvest00708-0284-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5125/370430/f40854018c49/jcinvest00708-0285-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5125/370430/87611b2718a3/jcinvest00708-0285-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5125/370430/a8c149bb9ccb/jcinvest00708-0287-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5125/370430/22432e54da17/jcinvest00708-0284-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5125/370430/f40854018c49/jcinvest00708-0285-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5125/370430/87611b2718a3/jcinvest00708-0285-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5125/370430/a8c149bb9ccb/jcinvest00708-0287-a.jpg

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本文引用的文献

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Evidence from radioligand assays that somatomedin-C and insulin-like growth factor-I are similar to each other and different from other somatomedins.放射配体分析的证据表明,生长调节素C和胰岛素样生长因子-I彼此相似,且与其他生长调节素不同。
J Clin Endocrinol Metab. 1980 Jan;50(1):206-8. doi: 10.1210/jcem-50-1-206.
2
Autoantibodies against the insulin receptor recognize the insulin binding subunits of an oligomeric receptor.抗胰岛素受体自身抗体可识别寡聚受体的胰岛素结合亚基。
Diabetes. 1981 Apr;30(4):354-7. doi: 10.2337/diab.30.4.354.
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Insulin resistance associated with androgen excess in women with autoantibodies to the insulin receptor.
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Biochem J. 1987 Jun 15;244(3):769-74. doi: 10.1042/bj2440769.
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