Glucokinase regulatory protein is essential for the proper subcellular localisation of liver glucokinase

Glucokinase regulatory protein is essential for the proper subcellular localisation of liver glucokinase
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DOI:
10.1016/s0014-5793(99)00971-0
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发表时间:
1999-08-06
期刊:
影响因子:
3.5
通讯作者:
Ferrer, JC
Ferrer, JC
中科院分区:
生物学3区
文献类型:
--
作者:
de la Iglesia, N;Veiga-da-Cunha, M;Ferrer, JC

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葡萄糖激酶(GK)是肝脏葡萄糖稳态反应中的关键酶,其细胞内定位取决于细胞的代谢状态。大鼠肝GK和非洲爪蟾GK,融合到绿色荧光蛋白(GFP),集中在细胞核培养的大鼠肝细胞在低葡萄糖和高葡萄糖易位到细胞质。三种突变形式的爪蟾GK与GK调节蛋白(GKRP)的亲和力降低没有集中在肝细胞核,即使在低葡萄糖。在COS-1和HeLa细胞中,蓝色荧光蛋白(BFP)标记的大鼠肝脏GK版本只有在与GKRP-GFP共表达时才能在细胞核中积累。在低葡萄糖时,两种蛋白质都集中在核区室中,而在高葡萄糖时,BFP-GK易位到细胞质中,而GKRP-GFP保留在核中。这些研究结果表明,GKRP的存在和结合是必要的和足够的适当的细胞内定位的CX和直接参与GK亚细胞分布的控制GKRP。(C)1999年欧洲生物化学学会联合会。
Glucokinase (GK), a key enzyme in the glucose homeostatic responses of the liver, changes its intracellular localisation depending on the metabolic status of the cell. Rat liver GK and Xenopus laevis GK, fused to the green fluorescent protein (GFP), concentrated in the nucleus of cultured rat hepatocytes at low glucose and translocated to the cytoplasm at high glucose. Three mutant forms of Xenopus GK with reduced affinity for GK regulatory protein (GKRP) did not concentrate in the hepatocyte nuclei, even at low glucose. In COS-1 and HeLa cells, a blue fluorescent protein (BFP)-tagged version of rat liver GK was only able to accumulate in the nucleus when it was co-expressed with GKRP-GFP. At low glucose, both proteins concentrated in the nuclear compartment and at high glucose, BFP-GK translocated to the cytosol while GKRP-GFP remained in the nucleus. These findings indicate that the presence of and binding to GKRP are necessary and sufficient for the proper intracellular localisation of CX and directly involve GKRP in the control of the GK subcellular distribution. (C) 1999 Federation of European Biochemical Societies.