A new pathway for synthesis of phosphatidylinositol-4,5-bisphosphate
A new pathway for synthesis of phosphatidylinositol-4,5-bisphosphate
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DOI：
10.1038/36621
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发表时间：
1997-11-13
期刊：
影响因子：
64.8
通讯作者：
Cantley, LC
中科院分区：
文献类型：
--
作者：
Rameh, LE;Tolias, KF;Cantley, LC
磷脂酰肌醇-4，5-二磷酸（PtdIns-4，5-P-2）是肌醇磷酸化信号通路中的关键分子，它是由肌醇环D-5位上的PtdIns-4-P磷酸化合成的。根据其酶性质和序列相似性，体外产生PtdInsP-4，5-P-2的酶分为两个相关的亚家族（I型和II型PtdInsP-5-OH激酶或PIP（5）Ks）（1）。在这里，我们重新研究了这些酶的底物特异性。正如预期的那样，I型酶在肌醇环的D-5位磷酸化PtdIns-4-P。令人惊讶的是，在某些组织中大量存在的II型酶在D-4位置磷酸化PtdIns-5-P，因此应被认为是4-OH激酶或PIP（4）K。早期的错误，在表征的II型酶的活性是由于污染PtdIns-5-P的商业制剂中的PtdIns-4-P的存在。虽然PtdIns-5-P以前被认为不存在于体内，我们发现这种脂质存在于哺乳动物成纤维细胞的证据，建立一个新的途径PtdIns-4，5-P-2的合成。
Phosphatidylinositol-4,5-bisphosphate (PtdIns-4,5-P-2), a key molecule in the phosphoinositide signalling-pathway, was thought to be synthesized exclusively by phosphorylation of PtdIns-4-P at the D-5 position of the inositol ring. The enzymes that produce PtdIns-4,5-P-2 in vitro fall into two related subfamilies (type I and type II PtdInsP-5-OH kinases, or PIP(5)Ks) based on their enzymatic properties and sequence similarities(1). Here we have reinvestigated the substrate specificities of these enzymes. As expected, the type I enzyme phosphorylates PtdIns-4-P at the D- 5 position of the inositol ring. Surprisingly, the type II enzyme, which is abundant in some tissues, phosphorylates PtdIns-5-P at the D-4 position, and thus should be considered as a 4-OH kinase, or PIP(4)K. The earlier error in characterizing the activity of the type II enzyme is due to the presence of contaminating PtdIns-5-P in commercial preparations of PtdIns-4-P. Although PtdIns-5-P was previously thought not to exist in vivo, we find evidence for the presence of this lipid in mammalian fibroblasts, establishing a new pathway for PtdIns-4,5-P-2 synthesis.