Type I phosphatidylinositol-4-phosphate 5-kinases are distinct members of this novel lipid kinase family
Type I phosphatidylinositol-4-phosphate 5-kinases are distinct members of this novel lipid kinase family
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DOI：
10.1074/jbc.271.51.32937
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发表时间：
1996-12-20
影响因子：
4.8
通讯作者：
Anderson, RA
中科院分区：
文献类型：
--
作者：
Loijens, JC;Anderson, RA
磷脂酰肌醇-4-磷酸5激酶（PIP5K）合成磷脂酰肌醇-4,5-二磷酸，这是磷脂酰肌醇信号传导的关键前体，也直接调节一些蛋白质和细胞过程。红细胞中有两种不同的PIP5Ks， 68 kDa I型（PIP5KI）和53 kDa II型（PIP5KII）亚型。利用红系68-kDa PIP5KI的肽序列，我们从人脑中分离出编码PIP5KI α的cdna。获得的第二种亚型PIP5KI β的部分cdna证实，人类STM7基因编码了一种以前未被识别的PIP5KI。然而，肽序列显示红系PIP5KI与PIP5KI α对应。重组、细菌表达的PIP5KI α具有PIP5K活性，对红系PIP5KI抗体有免疫反应。Northern分析发现，PIP5KI α和PIP5KI β在组织中分布广泛，但表达水平差异较大。PIP5KIs与PIP5KII α、酵母Mss4p和Fab1p的激酶结构域以及在数据库中发现的秀丽隐杆线虫fab1样蛋白具有同源性。这些新的异构体改进了PIP5K活性的序列要求，并可能调节这些酶。此外，PLP5KIs和PIP5KII α之间的有限同源性（几乎完全位于激酶结构域核心）为区分I型和II型PIP5Ks提供了分子基础。
Phosphatidylinositol-4-phosphate 5-kinases (PIP5K) synthesize phosphatidylinositol-4,5-bisphosphate, a key precursor in phosphoinositide signaling that also regulates some proteins and cellular processes directly. Two distinct PIP5Ks have been characterized in erythrocytes, the 68 kDa type I (PIP5KI) and 53-kDa type II (PIP5KII) isoforms. Using peptide sequences from the erythroid 68-kDa PIP5KI, we have isolated cDNAs encoding PIP5KI alpha from human brain. Partial cDNAs obtained for a second isoform, PIP5KI beta, established that the human STM7 gene encoded a previously unrecognized PIP5KI. However, the peptide sequences demonstrated that erythroid PIP5KI corresponded to PIP5KI alpha. Recombinant, bacterially expressed PIP5KI alpha possessed PIP5K activity and was immunoreactive with erythroid PIP5KI antibodies. By Northern analysis, PIP5KI alpha and PIP5KI beta had wide tissue distributions, but their expression levels differed greatly. PIP5KIs had homology to the kinase domains of PIP5KII alpha, yeast Mss4p and Fab1p, and a new Caenorhabditis elegans Fab1-like protein identified in the data base. These new isoforms have refined the sequence requirements for PIP5K activity and, potentially, regulation of these enzymes. Furthermore, the limited homology between PLP5KIs and PIP5KII alpha, which was almost exclusively within the kinase domain core, provided a molecular basis for distinction between type I and II PIP5Ks.