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人白血病淋巴母细胞上胰岛素、胰岛素样生长因子I和II以及生长激素受体的特性分析

Characterization of insulin, insulin-like growth factors I and II, and growth hormone receptors on human leukemic lymphoblasts.

作者信息

Lee P D, Rosenfeld R G, Hintz R L, Smith S D

出版信息

J Clin Endocrinol Metab. 1986 Jan;62(1):28-35. doi: 10.1210/jcem-62-1-28.

Abstract

Receptors for insulin, insulin-like growth factors I and II (IGF-I and IGF-II), and human GH were studied in 6 T- and 12 B-lymphoblast cell lines isolated from patients with lymphoid malignancies. These cell lines have been maintained in continuous culture with stable chromosome, immunophenotype, and enzyme characteristics for an 8- to 21-month period. Four of 6 T-cell lines expressed IGF-I, but not insulin, receptors. One T-cell line bound only insulin, and 1 T-cell line bound both hormones. Conversely, 9 of 12 B-cell lines had insulin, but not IGF-I, receptors. Two of these lines bound both hormones, and 1 line did not bind either hormone. IGF-II binding was less than 1.5%/10 million cells for all lines and was less than 1% for 13 of the 18 lines. Specific binding of GH was undetectable in all cell lines. Time, temperature, and pH dependence of peptide binding were characterized for the T-cell IGF-I receptor and the B-cell insulin receptor and were consistent with previously described models for these receptors. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the cross-linked receptors revealed an apparent mol wt greater than 300K unreduced and a 130K binding subunit after dithiothreitol reduction for both the T-cell IGF-I and the B-cell insulin receptor. These cell lines thus provided a unique opportunity for the study of growth factor receptors in fully characterized clonal populations of human lymphoblasts. We conclude that specific receptors for IGF-I and insulin are present on T- and B-lymphoblasts; divergence of these receptors appears to be a characteristic of lymphoblasts, since T-cells preferentially expressed IGF-I receptors and B-cells expressed insulin receptors; and IGF-II binding was relatively low, while specific GH binding was undetectable on both T- and B-lymphoblasts. These results suggest that insulin and IGF-I may play a role in lymphocyte differentiation and metabolism.

摘要

在从淋巴系统恶性肿瘤患者中分离出的6个T淋巴细胞系和12个B淋巴细胞系中,对胰岛素、胰岛素样生长因子I和II(IGF-I和IGF-II)以及人生长激素(GH)的受体进行了研究。这些细胞系在连续培养中已维持了8至21个月,具有稳定的染色体、免疫表型和酶特性。6个T细胞系中有4个表达IGF-I受体,但不表达胰岛素受体。1个T细胞系仅结合胰岛素,1个T细胞系结合两种激素。相反,12个B细胞系中有9个具有胰岛素受体,但不具有IGF-I受体。其中2个细胞系结合两种激素,1个细胞系两种激素均不结合。所有细胞系的IGF-II结合量均低于1.5%/1000万个细胞,18个细胞系中有13个低于1%。在所有细胞系中均未检测到GH的特异性结合。对T细胞IGF-I受体和B细胞胰岛素受体的肽结合的时间、温度和pH依赖性进行了表征,结果与先前描述的这些受体模型一致。经交联的受体的十二烷基硫酸钠-聚丙烯酰胺凝胶电泳显示,T细胞IGF-I受体和B细胞胰岛素受体在未还原时的表观分子量均大于300K,在二硫苏糖醇还原后有一个130K的结合亚基。因此,这些细胞系为在充分表征的人淋巴母细胞克隆群体中研究生长因子受体提供了独特的机会。我们得出结论,IGF-I和胰岛素的特异性受体存在于T和B淋巴母细胞上;这些受体的差异似乎是淋巴母细胞的一个特征,因为T细胞优先表达IGF-I受体,而B细胞表达胰岛素受体;IGF-II结合相对较低,而在T和B淋巴母细胞上均未检测到特异性GH结合。这些结果表明,胰岛素和IGF-I可能在淋巴细胞分化和代谢中起作用。

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