Erneux C, Govaerts C, Communi D, Pesesse X
Interdisciplinary Research Institute (IRIBHN), Université Libre de Bruxelles, Campus Erasme Building C, 808 Route de Lennik, B-1070 Brussels, Belgium.
Biochim Biophys Acta. 1998 Dec 8;1436(1-2):185-99. doi: 10.1016/s0005-2760(98)00132-5.
Distinct forms of inositol and phosphatidylinositol polyphosphate 5-phosphatases selectively remove the phosphate from the 5-position of the inositol ring from both soluble and lipid substrates, i.e., inositol 1,4,5-trisphosphate (Ins(1,4,5)P3), inositol 1,3,4, 5-tetrakisphosphate (Ins(1,3,4,5)P4), phosphatidylinositol 4, 5-bisphosphate (PtdIns(4,5)P2) or phosphatidylinositol 3,4, 5-trisphosphate (PtdIns(3,4,5)P3). In mammalian cells, this family contains a series of distinct genes and splice variants. All inositol polyphosphate 5-phosphatases share a 5-phosphatase domain and various protein modules probably responsible for specific cell localisation or recruitment (SH2 domain, proline-rich sequences, prenylation sites, etc.). Type I Ins(1,4,5)P3 5-phosphatase also uses Ins(1,3,4,5)P4 but not the phosphoinositides as substrates. This enzyme is targeted to specific membranes by means of a prenylation site. Type II 5-phosphatases can use both PtdIns(4,5)P2 and PtdIns(3,4,5)P3 as substrates. Five mammalian enzymes and multiple splice variants are known: INPP5P or inositol polyphosphate 5-phosphatase II, OCRL (a Golgi protein implicated in the Lowe oculocerebrorenal syndrome), synaptojanin (a protein involved in the recycling of synaptic vesicles), SHIP 1 and SHIP 2 (or SH2-containing inositol 5-phosphatases). As discussed in this review, the substrate specificity, regulatory mechanisms, subcellular localisation and tissue specificity indicate that the different 5-phosphatase isoforms may play specific roles. As known in the dephosphorylation of tyrosine containing substrates by the tyrosine protein phosphatases or in the metabolism of cyclic nucleotides by the cyclic nucleotide phosphodiesterases, inositol polyphosphate 5-phosphatases directly participate in the control of second messengers in response to both activation or inhibitory cell signalling.
不同形式的肌醇和磷脂酰肌醇多磷酸5-磷酸酶可选择性地从可溶性和脂质底物的肌醇环5位去除磷酸基团，即肌醇1,4,5-三磷酸（Ins(1,4,5)P3）、肌醇1,3,4,5-四磷酸（Ins(1,3,4,5)P4）、磷脂酰肌醇4,5-二磷酸（PtdIns(4,5)P2）或磷脂酰肌醇3,4,5-三磷酸（PtdIns(3,4,5)P3）。在哺乳动物细胞中，该家族包含一系列不同的基因和剪接变体。所有肌醇多磷酸5-磷酸酶都共享一个5-磷酸酶结构域和各种可能负责特定细胞定位或募集的蛋白质模块（SH2结构域、富含脯氨酸的序列、异戊二烯化位点等）。I型肌醇1,4,5-三磷酸5-磷酸酶也以肌醇1,3,4,5-四磷酸为底物，但不以磷酸肌醇为底物。该酶通过异戊二烯化位点靶向特定膜。II型5-磷酸酶可同时以磷脂酰肌醇4,5-二磷酸和磷脂酰肌醇3,4,5-三磷酸为底物。已知有五种哺乳动物酶和多种剪接变体：INPP5P或肌醇多磷酸5-磷酸酶II、OCRL（一种与Lowe眼脑肾综合征有关的高尔基体蛋白）、突触素（一种参与突触小泡再循环的蛋白质）、SHIP 1和SHIP 2（或含SH2的肌醇5-磷酸酶）。如本综述所述，底物特异性、调节机制、亚细胞定位和组织特异性表明不同的5-磷酸酶同工型可能发挥特定作用。正如酪氨酸蛋白磷酸酶对含酪氨酸底物的去磷酸化或环核苷酸磷酸二酯酶对环核苷酸的代谢一样，肌醇多磷酸5-磷酸酶直接参与响应激活或抑制性细胞信号传导对第二信使的控制。
