Activation of protein kinase C by phosphatidylinositol 3,4,5-trisphosphate.
Activation of protein kinase C by phosphatidylinositol 3,4,5-trisphosphate.
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磷脂酰肌醇 3,4,5-三磷酸激活蛋白激酶 C。
DOI：
10.1006/bbrc.1993.2016
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发表时间：
1993
影响因子：
3.1
通讯作者：
Chauhan,VP
中科院分区：
文献类型：
--
作者：
Singh,SS;Chauhan,A;Brockerhoff,H;Chauhan,VP
从大鼠肝胞液中部分纯化了磷脂酰肌醇3-激酶（PI 3-kinase），并以磷脂酰肌醇4，5-二磷酸（PIP 2）为底物合成了磷脂酰肌醇3，4，5-三磷酸（PIP 3）。纯化的PIP 3（不含层析草酸盐）在磷脂酰丝氨酸和钙（PKC辅因子）存在下以浓度依赖性方式激活蛋白激酶C（PKC）。在缺乏这些辅因子的情况下，未观察到PIP 3的作用。比较PIP 3和PIP 2对PKC活性的影响表明，PIP 3是比PIP 2更有效的PKC激活剂。PKC与PIP 3的亲和力比与PIP 2的亲和力高4倍（KPIP 3 = 0.022mol%，KPIP 2 = 0.087mol%），而其最大速率（Vmax）与PIP 2刺激的PKC活性相似（0.4 - 0.5 μmol/mg/min）。这些结果表明PIP 3在信号转导中的生理作用，并支持先前的发现（Chauhan等（1991）Arch.Biochem.Biophys.2001）。287，283），磷酸肌醇类的PKC激活随着这些脂质的磷酸化状态而增加。我们认为PIP 3通过激活PKC可能启动了一个级联反应，从PIP 3 → PKC激活→影响其他蛋白激酶如MAP激酶→基因表达。
Phosphatidylinositol 3-kinase (PI 3-kinase) was partially purified from rat liver cytosol and used to synthesize phosphatidylinositol 3,4,5-trisphosphate (PIP3), using phosphatidylinositol 4,5-bisphosphate (PIP2) as a substrate. Purified PIP3(free of chromatographic oxalate) activated protein kinase C (PKC) in the presence of phosphatidylserine and calcium (PKC-cofactors) in a concentration-dependent manner. In the absence of these cofactors, effect of PIP3was not observed. Comparison of the effects of PIP3and PIP2on PKC activity indicates that PIP3is a more potent PKC-activator than PIP2. The affinity of PKC to PIP3was 4 fold higher than that to PIP2(KPIP3= 0.022 and KPIP2= 0.087 mol %), while its maximal velocity (Vmax) was similar to that of PIP2-stimulated PKC activity (0.4 - 0.5 μmol/mg/min). These results suggest a physiological role for PIP3in signal transduction, and support the previous finding (Chauhan et al. (1991) Arch. Biochem. Biophys. 287,283) that PKC-activation by phosphoinositides increases with the state of phosphorylation of these lipids. We propose that PIP3by activating PKC may initiate a cascade of events from PIP3→ PKC-activation → effects on other protein kinases such as MAP-kinase → gene expression.