Dephosphorylation of myo-inositol 1,4,5-trisphosphate and myo-inositol 1,3,4-triphosphate.
Dephosphorylation of myo-inositol 1,4,5-trisphosphate and myo-inositol 1,3,4-triphosphate.
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肌醇 1,4,5-三磷酸和肌醇 1,3,4-三磷酸的去磷酸化。
DOI：
10.1042/bj2420393
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发表时间：
1987
期刊：
影响因子：
--
通讯作者：
C. Kirk
中科院分区：
文献类型：
--
作者：
S. Shears;D. J. Storey;A. Morris;A. B. Cubitt;J. B. Parry;R. Michell;C. Kirk
我们扩大了我们以前的研究[Storey，Shears，Kirk&Micell(1984)Nature(London)312,374-376]，研究了Ins(1，4，5)P3(肌醇1，4，5-三磷酸)磷酸酶在大鼠肝脏和人红细胞中的亚细胞定位和性质。我们还研究了INS(1，3，4)P3(肌醇1，3，4-三磷酸)在大鼠肝脏中的代谢。膜结合和胞质INS(1，4，5)P3磷酸酶都攻击5-磷酸。膜结合酶位于质膜的内表面，与高尔基体结合的活性很少或没有。胞质Ins(1，4，5)P3 5-磷酸酶(Mr 77000)通过凝胶过滤从Ins(1，4)P2(1，4-二磷酸肌醇)和1-磷酸肌醇磷酸酶(Mr 54000)中分离出来。INS(1，4，5)P35-磷酸酶活性不受胰岛素、加压素、胰高血糖素和二丁酰环腺苷处理的影响。细胞匀浆中Ins(1，4，5)P35-磷酸酶活性不受[Ca~(2+)]从0.1微米到2微米变化的影响。在100000 g的肝匀浆离心后，Ins(1，3，4)P3磷酸酶活性主要局限于上清液中。上清液和颗粒中的活性总和超过原始匀浆中的活性总和。当这些组分重组时，INS(1，3，4)P3磷酸酶活性恢复到未分离的匀浆中观察到的活性。Ins(1，3，4，5)P3是由Ins(1，3，4，5)P4(肌醇1，3，4，5-四磷酸)合成的，它被代谢成新的InsP2，即3，4-异构体。50 mM-Li+或0.07 mM-Ins(1，4)P2单独作用对INS(1，3，4)P3磷酸酶活性无明显影响，但联合使用时可抑制INS(1，3，4)P3代谢。在Li+处理和加压素刺激的肝细胞中，Ins(1，4)P2的浓度可能达到足以抑制Ins(1，3，4)P3代谢的浓度，而对Ins(1，4，5)P3的降解几乎没有影响。
We have augmented our previous studies [Storey, Shears, Kirk & Michell (1984) Nature (London) 312, 374-376] on the subcellular location and properties of Ins(1,4,5)P3 (inositol 1,4,5-trisphosphate) phosphatases in rat liver and human erythrocytes. We also investigate Ins(1,3,4)P3 (inositol 1,3,4-trisphosphate) metabolism by rat liver. Membrane-bound and cytosolic Ins(1,4,5)P3 phosphatases both attack the 5-phosphate. The membrane-bound enzyme is located on the inner face of the plasma membrane, and there is little or no activity associated with Golgi apparatus. Cytosolic Ins(1,4,5)P3 5-phosphatase (Mr 77,000) was separated by gel filtration from Ins(1,4)P2 (inositol 1,4-bisphosphate) and inositol 1-phosphate phosphatases (Mr 54,000). Ins(1,4,5)P3 5-phosphatase activity in hepatocytes was unaffected by treatment of the cells with insulin, vasopressin, glucagon or dibutyryl cyclic AMP. Ins(1,4,5)P3 5-phosphatase activity in cell homogenates was unaffected by changes in [Ca2+] from 0.1 to 2 microM. After centrifugation of a liver homogenate at 100,000 g, Ins(1,3,4)P3 phosphatase activity was largely confined to the supernatant. The sum of the activities in the supernatant and the pellet exceeded that in the original homogenate. When these fractions were recombined, Ins(1,3,4)P3 phosphatase activity was restored to that observed in unfractionated homogenate. Ins(1,3,4)P3 was produced from Ins(1,3,4,5)P4 (inositol 1,3,4,5-tetrakisphosphate) and was metabolized to a novel InsP2 that was the 3,4-isomer. Ins(1,3,4)P3 phosphatase activity was not changed by 50 mM-Li+ or 0.07 mM-Ins(1,4)P2 alone, but when added together these agents inhibited Ins(1,3,4)P3 metabolism. In Li+-treated and vasopressin-stimulated hepatocytes, Ins(1,4)P2 may reach concentrations sufficient to inhibit Ins(1,3,4)P3 metabolism, with little effect on Ins(1,4,5)P3 hydrolysis.