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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >CAMP- AND RAPAMYCIN-SENSITIVE REGULATION OF THE ASSOCIATION OF EUKARYOTIC INITIATION FACTOR 4E AND THE TRANSLATIONAL REGULATOR PHAS-I IN AORTIC SMOOTH MUSCLE CELLS
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CAMP- AND RAPAMYCIN-SENSITIVE REGULATION OF THE ASSOCIATION OF EUKARYOTIC INITIATION FACTOR 4E AND THE TRANSLATIONAL REGULATOR PHAS-I IN AORTIC SMOOTH MUSCLE CELLS

机译:主动脉平滑肌细胞中真核细胞起始因子4E和翻译调节物PHAS-I对CAMP和Rapamycin的敏感性调节

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摘要

Incubating rat aortic smooth muscle cells with either platelet-derived growth factor B (PDGF) or insulin-like growth factor I (IGF-I) increased the phosphorylation of PHAS-I, an inhibitor of the mRNA cap binding protein, eukaryotic initiation factor (eIF) 4E, Phosphorylation of PHAS-I promoted dissociation of the PHAS-I-eIF-4E complex, an effect that could partly explain the stimulation of protein synthesis by the two growth factors. Increasing cAMP with forskolin decreased PHAS-I phosphorylation and markedly increased the amount of eIF-4E bound to PHAS-I, effects consistent with an action of cAMP to inhibit protein synthesis. Both PDGF and IGF-I activated p70(S6K), but only PDGF increased mitogen-activated protein kinase activity, Forskolin decreased by 50% the effect of PDGF on increasing p70(S6K), and forskolin abolished the effect of IGF-I on the kinase. The effects of PDGF and IGF-I on increasing PHAS-I phosphorylation, on dissociating the PHAS-I-eIF-4E complex, and on increasing p70(S6K) were abolished by rapamycin, The results indicate that IGF-I and PDGF increase PHAS-I phosphorylation in smooth muscle cells by the same rapamycin-sensitive pathway that leads to activation of p70(S6K). [References: 39]
机译:将大鼠主动脉平滑肌细胞与血小板源性生长因子B(PDGF)或胰岛素样生长因子I(IGF-I)一起孵育可增加PHAS-I的磷酸化,PHAS-I是一种mRNA帽结合蛋白,真核起始因子( eIF)4E,PHAS-1的磷酸化促进了PHAS-1-eIF-4E复合物的解离,这种作用可以部分解释两个生长因子对蛋白质合成的刺激。用毛喉素增加cAMP可以减少PHAS-1的磷酸化,并显着增加与PHAS-1结合的eIF-4E的量,其作用与cAMP抑制蛋白质合成的作用一致。 PDGF和IGF-I均可激活p70(S6K),但只有PDGF可增加促分裂原激活的蛋白激酶活性,福司可林将PDGF对增加p70(S6K)的作用降低了50%,而福司可林取消了IGF-I对P70(S6K)的作用。激酶。雷帕霉素消除了PDGF和IGF-I对增加PHAS-I磷酸化,解离PHAS-I-eIF-4E复合物以及对增加p70(S6K)的影响,结果表明IGF-I和PDGF增加了PHAS -I通过相同的雷帕霉素敏感途径在平滑肌细胞中磷酸化,从而激活p70(S6K)。 [参考:39]

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