Guanine nucleotide and pyrophosphate activate exogenous phosphatidylinositol 4,5-bisphosphate hydrolysis in rat liver plasma membranes.

Guanine nucleotide and pyrophosphate activate exogenous phosphatidylinositol 4,5-bisphosphate hydrolysis in rat liver plasma membranes.
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鸟嘌呤核苷酸和焦磷酸激活大鼠肝质膜中的外源磷脂酰肌醇 4,5-二磷酸水解。

DOI:
10.1016/s0006-291x(87)80182-1
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发表时间:
1987
影响因子:
3.1
通讯作者:
Fain,JN
Fain,JN
中科院分区:
生物学4区
文献类型:
--
作者:
Bojanic,D;Wallace,MA;Wojcikiewicz,RJ;Fain,JN

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5'-鸟苷酰亚胺二磷酸 (GppNHp) 在脱氧胆酸盐存在下,刺激大鼠肝质膜中外源性 [3H] 磷脂酰肌醇 4,5-二磷酸 ([3H]PIP2) 经磷脂酶 C 介导的水解为肌醇 1,4,5-三磷酸。鸟嘌呤核苷酸的激活并不具有特异性,因为 5'-腺苷酰亚胺二磷酸、亚胺二磷酸和焦磷酸以相似的功效和效力刺激酶。当使用 [3H]PIP2 作为底物时,GppNHp 的酶激活最为明显。 [3H]PIP2 分解不需要添加 Ca++,但二价离子螯合剂会抑制水解。在存在 Ca++ 或 Mg++ 以及部分抑制酶的螯合剂浓度的情况下,GppNHp 刺激是明显的,表明这种效应并非归因于这些二价阳离子对酶或底物的亲和力的变化。这些结果表明,鸟嘌呤核苷酸可以通过非特异性作用刺激大鼠肝膜中外源性[3H]PIP2的水解,这可能是由于二磷酸部分与酶或底物的相互作用所致。
5′-guanylylimidodiphosphate (GppNHp), in the presence of deoxycholate, stimulated the phospholipase C-mediated hydrolysis of exogenous [3H]phosphatidylinositol 4,5-bisphosphate ([3H]PIP2) to myo-[3H]inositol 1,4,5-trisphosphate in rat liver plasma membranes. Activation was not specific for guanine nucleotides as 5′-adenylylimidodiphosphate, imidodiphosphate and pyrophosphate stimulated the enzyme with similar efficacies and potencies. Enzyme activation by GppNHp was most pronounced when [3H]PIP2was used as substrate. No added Ca++was required for [3H]PIP2breakdown but hydrolysis was inhibited by divalent ion chelators. GppNHp stimulation was apparent in the presence of Ca++or Mg++as well as chelator concentrations that partially inhibited the enzyme, indicating that this effect was not attributed to changes in affinity of these divalent cations for the enzyme or substrate. These results suggest that guanine nucleotides can stimulate the hydrolysis of exogenous [3H]PIP2in rat liver membranes by a non-specific effect probably due to the interaction of the diphosphate moiety with the enzyme or substrate.