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首页> 外文期刊>Molecular and Cellular Biology >Insulin Receptor Isoform A, a Newly Recognized, High-Affinity Insulin-Like Growth Factor II Receptor in Fetal and Cancer Cells
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Insulin Receptor Isoform A, a Newly Recognized, High-Affinity Insulin-Like Growth Factor II Receptor in Fetal and Cancer Cells

机译：胰岛素受体同工型A，一种新近公认的胎儿和癌细胞中高亲和力的胰岛素样生长因子II受体

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Insulin-like growth factor II (IGF-II) is a peptide growth factor that is homologous to both insulin-like growth factor I (IGF-I) and insulin and plays an important role in embryonic development and carcinogenesis. IGF-II is believed to mediate its cellular signaling via the transmembrane tyrosine kinase type 1 insulin-like growth factor receptor (IGF-I-R), which is also the receptor for IGF-I. Earlier studies with both cultured cells and transgenic mice, however, have suggested that in the embryo the insulin receptor (IR) may also be a receptor for IGF-II. In most cells and tissues, IR binds IGF-II with relatively low affinity. The IR is expressed in two isoforms (IR-A and IR-B) differing by 12 amino acids due to the alternative splicing of exon 11. In the present study we found that IR-A but not IR-B bound IGF-II with an affinity close to that of insulin. Moreover, IGF-II bound to IR-A with an affinity equal to that of IGF-II binding to the IGF-I-R. Activation of IR-A by insulin led primarily to metabolic effects, whereas activation of IR-A by IGF-II led primarily to mitogenic effects. These differences in the biological effects of IR-A when activated by either IGF-II or insulin were associated with differential recruitment and activation of intracellular substrates. IR-A was preferentially expressed in fetal cells such as fetal fibroblasts, muscle, liver and kidney and had a relatively increased proportion of isoform A. IR-A expression was also increased in several tumors including those of the breast and colon. These data indicate, therefore, that there are two receptors for IGF-II, both IGF-I-R and IR-A. Further, they suggest that interaction of IGF-II with IR-A may play a role both in fetal growth and cancer biology.
机译：胰岛素样生长因子II（IGF-II）是与胰岛素样生长因子I（IGF-I）和胰岛素都同源的肽生长因子，并且在胚胎发育和癌变中起重要作用。据信IGF-II通过跨膜酪氨酸激酶1型胰岛素样生长因子受体（IGF-I-R）介导其细胞信号转导，它也是IGF-I的受体。然而，对培养的细胞和转基因小鼠的早期研究表明，在胚胎中，胰岛素受体（IR）也可能是IGF-II的受体。在大多数细胞和组织中，IR以相对较低的亲和力结合IGF-II。由于外显子11的选择性剪接，IR以两种同工型（IR-A和IR-B）表达，相差12个氨基酸。在本研究中，我们发现IR-A结合IGF-II而不与IGF-II结合。接近胰岛素的亲和力。此外，IGF-II以与IGF-II与IGF-I-R结合的亲和力相等的亲和力与IR-A结合。胰岛素激活IR-A主要导致代谢作用，而IGF-II激活IR-A主要导致促有丝分裂作用。当被IGF-II或胰岛素激活时，IR-A的生物学效应的这些差异与细胞内底物的不同募集和激活有关。 IR-A优先在胎儿细胞如胎儿成纤维细胞，肌肉，肝脏和肾脏中表达，并且同工型A的比例相对增加。IR-A表达在包括乳腺和结肠癌在内的一些肿瘤中也增加。因此，这些数据表明IGF-II有两种受体，即IGF-I-R和IR-A。此外，他们认为IGF-II与IR-A的相互作用可能在胎儿生长和癌症生物学中均发挥作用。

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