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肌醇多磷酸5-磷酸酶:交通管制员、腰围守护者和肿瘤抑制因子?

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

作者信息

Astle Megan V, Horan Kristy A, Ooms Lisa M, Mitchell Christina A

机构信息

Department of Biochemistry and Molecular Biology Monash University, Clayton, Victoria, Australia, 3800.

出版信息

Biochem Soc Symp. 2007(74):161-81. doi: 10.1042/BSS0740161.

DOI:10.1042/BSS0740161
PMID:17233589
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.

摘要

磷酸肌醇信号调节细胞增殖、分化、细胞骨架重排和细胞内运输。肌醇多磷酸5-磷酸酶对磷脂酰肌醇-4,5-二磷酸(PtdIns(4,5)P2)和磷脂酰肌醇-3,4,5-三磷酸(PtdIns(3,4,5)P3)的水解作用调节突触小泡循环(突触素-1)、造血细胞功能[含SH2结构域的肌醇多磷酸5-磷酸酶-1(SHIP1)]、肾细胞功能[劳氏眼脑肾综合征(OCRL)]和胰岛素信号传导(SHIP2)。在此,我们对十种哺乳动物5-磷酸酶的特性进行详细综述。基因敲除小鼠的表型及表达不足研究均与显著的表型变化相关,这表明尽管在许多情况下底物特异性和组织表达存在重叠,但它们具有非冗余作用。磷酸肌醇信号传导控制方面的异常复杂性仍在不断被揭示。

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