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首页> 外文期刊>Cellular Signalling >IRS-4 mediated mitogenic signalling by insulin and growth hormone in LB cells, a murine T-cell lymphoma devoid of IGF-I receptors
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IRS-4 mediated mitogenic signalling by insulin and growth hormone in LB cells, a murine T-cell lymphoma devoid of IGF-I receptors

机译:IRS-4通过胰岛素和生长激素介导的LB细胞(不含IGF-1受体的鼠类T细胞淋巴瘤)介导有丝分裂信号

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Insulin and growth hormone (GH) induce mitogenic and metabolic signals in cells, GH either directly or indirectly via IGF-I production. We have studied a spontaneous murine T-cell lymphoma (LB cells) devoid of IGF-I receptors in which proliferation is maintained by insulin [Int. J. Cancer 50 (1992) 80], and show that GH is more potent than insulin, with both GH and insulin dose-response curves for thymidine incorporation being bell-shaped. Binding showed somatogenic rather than lactogenic GH receptors. Insulin stimulated phosphorylation of the insulin receptor and of a 160-kDa protein, identified as the IRS-4 protein. This phosphorylated IRS-4 associated with PI3-kinase, which was activated along with the downstream p70(S6) kinase, whereas the Ras-MAPK pathway was not. Using selective inhibitors, the PI3-kinase, but not p70(S6) kinase or MEK, was found to be involved in insulin-stimulated DNA synthesis. GH induced tyrosine phosphorylation of IRS-4 and nuclear translocation of STAT5. The LB cells constitute a new model for studying GH and insulin signalling without interference of IGF-I receptors. (C) 2002 Elsevier Science Inc. All rights reserved. [References: 55]
机译:胰岛素和生长激素(GH)直接或间接通过IGF-I产生诱导细胞中的促有丝分裂和代谢信号。我们已经研究了缺乏IGF-I受体的自发鼠T细胞淋巴瘤(LB细胞),其中胰岛素可以维持增殖[Int。 J.Cancer 50(1992)80],并且表明GH比胰岛素更有效,胸苷掺入的GH和胰岛素剂量反应曲线均为钟形。结合显示出生体而不是生乳的GH受体。胰岛素刺激胰岛素受体和160kDa蛋白质(称为IRS-4蛋白质)的磷酸化。这种磷酸化的IRS-4与PI3-激酶相关,后者与下游的p70(S6)激酶一起被激活,而Ras-MAPK途径则未被激活。使用选择性抑制剂,发现PI3-激酶而不是p70(S6)激酶或MEK与胰岛素刺激的DNA合成有关。 GH诱导了IRS-4的酪氨酸磷酸化和STAT5的核易位。 LB细胞构成了研究GH和胰岛素信号转导而又不干扰IGF-I受体的新模型。 (C)2002 Elsevier Science Inc.保留所有权利。 [参考:55]

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