微分调节phosphoglucose异构酶/自分泌运动因子活动由蛋白激酶CK2磷酸化。
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Yanagawa T, Funasaka T,堤,拉兹T,田中N,拉兹
微分调节phosphoglucose异构酶/自分泌运动因子活动由蛋白激酶CK2磷酸化。
J生物化学杂志。2005年3月18日,280(11):10419 - 26所示。2005年1月5 Epub。
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15637053 (在PubMed]
- 文摘
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Phosphoglucose异构酶(PGI;EC 5.3.1.9)是一种胞质管家糖代谢途径的酶在糖酵解和糖质新生中发挥着关键作用。PGI是一种多功能二聚的蛋白,细胞行为与特性,包括自分泌细胞因子活性因子(AMF)诱发促有丝分裂的,motogenic,和分化功能,PGI已经涉及到肿瘤的进展和转移。鲜为人知的生化PGI / AMF的监管活动,尽管众所周知,人类PGI / AMF在Ser(185)磷酸化蛋白激酶CK2 (CK2);然而,这种磷酸化的生理意义是未知的。因此,通过定点诱变,我们与天冬氨酸取代Ser (185) (S185D)或谷氨酸(S185E),介绍了一个负电荷和构象变化,模拟磷酸化。Ser-to-Ala突变蛋白(S185A)是废除磷酸化生成的。生化分析表明,突变的蛋白质磷酸化PGI展出酶活性下降,而S185A突变PGI蛋白质保留完整的酶活性。PGI磷酸化酶活性的CK2也导致下调。此外,CK2击倒的RNA干扰与老年病有关细胞PGI酶活性。 The three recombinant mutant proteins exhibited indistinguishable cytokine activity and receptor-binding affinities compared with the wild-type protein. In both in vitro and in vivo assays, the wild-type and S185A mutant proteins underwent active species dimerization, whereas both the S185D and S185E mutant proteins also formed tetramers. These results demonstrate that phosphorylation affects the allosteric kinetic properties of the enzyme, resulting in a less active form of PGI, whereas non-phosphorylated protein species retain cytokine activity. The process by which phosphorylation modulates the enzymatic activity of PGI thus has an important implication for the understanding of the biological regulation of this key glucose metabolism-regulating enzyme.