The inositol polyphosphate 5-phosphatases: traffic controllers, waistline watchers and tumour suppressors?

Megan V Astle, Kristy A Horan, Lisa M Ooms, Christina A Mitchell
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引用次数: 59

Abstract

Phosphoinositide signals regulate cell proliferation, differentiation, cytoskeletal rearrangement and intracellular trafficking. Hydrolysis of PtdIns(4,5)P2 and PtdIns(3,4,5)P3, by inositol polyphosphate 5-phosphatases regulates synaptic vesicle recycling (synaptojanin-1), hematopoietic cell function [SHIP1(SH2-containing inositol polyphosphate 5-phosphatase-1)], renal cell function [OCRL (oculocerebrorenal syndrome of Lowe)] and insulin signalling (SHIP2). We present here a detailed review of the characteristics of the ten mammalian 5-phosphatases. Knockout mouse phenotypes and underexpression studies are associated with significant phenotypic changes, indicating non-redundant roles, despite, in many cases, overlapping substrate specificity and tissue expression. The extraordinary complexity in the control of phosphoinositide signalling continues to be revealed.

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肌醇聚磷酸5-磷酸酶:交通控制者、腰围控制者和肿瘤抑制者?
磷酸肌肽信号调节细胞增殖、分化、细胞骨架重排和细胞内运输。肌醇多磷酸5-磷酸酶水解PtdIns(4,5)P2和PtdIns(3,4,5)P3可调节突触囊泡循环(synaptojanin-1)、造血细胞功能[SHIP1(含肌醇多磷酸5-磷酸酶-1)]、肾细胞功能[ocl (ocococerebrorenal syndrome of Lowe)]和胰岛素信号传导(SHIP2)。我们在这里详细回顾了10种哺乳动物5-磷酸酶的特征。敲除小鼠表型和低表达研究与显著的表型变化相关,表明尽管在许多情况下,底物特异性和组织表达重叠,但它们的作用并非冗余。磷脂肌苷信号传导控制的异常复杂性继续被揭示。
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Pleckstrin homology (PH) domains and phosphoinositides. Evolutionarily conserved structural and functional roles of the FYVE domain. The role of the phosphoinositides at the Golgi complex. PtdIns5P: a little phosphoinositide with big functions? Our FABulous VACation: a decade of phosphatidylinositol 3,5-bisphosphate.
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