Thomas Mark P, Erneux Christophe, Potter Barry V L
Department of Pharmacy and Pharmacology, University of Bath, Claverton Down, Bath, BA2 7AY, UK.
I.R.I.B.H.M., Université Libre de Bruxelles, Campus Erasme, 808 Route de Lennik, 1070, Brussels, Belgium.
Chembiochem. 2017 Feb 1;18(3):233-247. doi: 10.1002/cbic.201600541. Epub 2017 Jan 10.
SHIP2 is a phosphatase that acts at the 5-position of phosphatidylinositol 3,4,5-trisphosphate. It is one of several enzymes that catalyse dephosphorylation at the 5-position of phosphoinositides or inositol phosphates. SHIP2 has a confirmed role in opsismodysplasia, a disease of bone development, but also interacts with proteins involved in insulin signalling, cytoskeletal function (thus having an impact on endocytosis, adhesion, proliferation and apoptosis) and immune system function. The structure of three domains (constituting about 38 % of the protein) is known. Inhibitors of SHIP2 activity have been designed to interact with the catalytic domain with sub-micromolar IC values: these come from a range of structural classes and have been shown to have in vivo effects consistent with SHIP2 inhibition. Much remains unknown about the roles of SHIP2, and possible future directions for research are indicated.
SHIP2是一种作用于磷脂酰肌醇3,4,5-三磷酸5位的磷酸酶。它是几种催化磷酸肌醇或肌醇磷酸5位去磷酸化的酶之一。SHIP2在骨发育疾病骨发育不全中具有确定的作用，但也与参与胰岛素信号传导、细胞骨架功能（从而影响内吞作用、黏附、增殖和凋亡）以及免疫系统功能的蛋白质相互作用。已知三个结构域（约占蛋白质的38%）的结构。已设计出SHIP2活性抑制剂，使其与催化结构域相互作用，IC值为亚微摩尔级：这些抑制剂来自一系列结构类别，并已证明具有与SHIP2抑制作用一致的体内效应。关于SHIP2的作用仍有许多未知之处，并指出了未来可能的研究方向。
