PLATELET-DERIVED GROWTH-FACTOR STIMULATES SYNTHESIS OF PTDLNS(3,4,5)P3 BY ACTIVATING A PTDLNS(4,5)P2 3-OH KINASE
PLATELET-DERIVED GROWTH-FACTOR STIMULATES SYNTHESIS OF PTDLNS(3,4,5)P3 BY ACTIVATING A PTDLNS(4,5)P2 3-OH KINASE
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DOI：
10.1038/358157a0
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发表时间：
1992-07-09
期刊：
影响因子：
64.8
通讯作者：
STEPHENS, LR
中科院分区：
文献类型：
--
作者：
HAWKINS, PT;JACKSON, TR;STEPHENS, LR
尽管已知3-磷酸化肌醇脂质的酶刺激合成形成细胞内信号系统1-5，但对该途径中的关键受体调节事件没有共识，并且仍然不清楚哪种中间体代表潜在的输出信号。我们在这里表明，在血小板衍生生长因子刺激的3 T3细胞中3-磷酸化肌醇脂质合成的关键步骤是磷脂酰肌醇（4，5）-二磷酸（3）-羟基（PtdIns（4，5）P2 3-OH）激酶的激活。类似的结论已被应用于解释甲酰基-Met-Leu-Phe对中性粒细胞的作用6，并且可能是通过内在酪氨酸激酶或通过G蛋白偶联的受体刺激3-磷酸化肌醇脂质代谢中的相同步骤。PtdIns（4，5）P2 3-OH激酶激活的这两种机制与另一种关键信号酶磷脂酶C（参考文献7）的激活机制之间的密切相似性，使人们关注PtdIns（4，5）P，3-OH激酶的产物PtdIns（3，4，5）P3作为可能的新第二信使。
ALTHOUGH the hormone-stimulated synthesis of 3-phosphorylated inositol lipids is known to form an intracellular signalling system 1-5, there is no consensus on the crucial receptor-regulated event in this pathway and it is still not clear which of the intermediates represent potential output signals. We show here that the key step in the synthesis of 3-phosphorylated inositol lipids in 3T3 cells stimulated by platelet-derived growth factor is the activation of a phosphatidylinositol(4,5)-bisphosphate (3)-hydroxy (PtdIns(4,5)P2 3-OH) kinase. A similar conclusion has been applied to explain the actions of formyl-Met-Leu-Phe on neutrophils 6, and it may be that receptors that couple through intrinsic tyrosine kinases or through G proteins stimulate the same step in 3-phosphorylated inositol lipid metabolism. The close parallel between these two mechanisms for the activation of PtdIns(4,5)P2 3-OH kinase and those described for the activation of another key signalling enzyme, phospholipase C (ref. 7), focuses attention on the product of the PtdIns(4,5)P, 3-OH kinase, PtdIns(3,4,5)P3, as a possible new second messenger.