Regulation of myotubularin-related (MTMR)2 phosphatidylinositol phosphatase by MTMR5, a catalytically inactive phosphatase
Regulation of myotubularin-related (MTMR)2 phosphatidylinositol phosphatase by MTMR5, a catalytically inactive phosphatase
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DOI：
10.1073/pnas.0431052100
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发表时间：
2003-04-15
影响因子：
11.1
通讯作者：
Dixon, JE
中科院分区：
文献类型：
--
作者：
Kim, SA;Vacratsis, PO;Dixon, JE
肌管蛋白（MTM）家族是真核生物中最保守的蛋白酪氨酸磷酸酶亚家族之一。MTM 1是该家族的原型成员，在X连锁肌管性肌病中发生突变，而MTM相关（MTMR）2基因的突变导致4 B1型Charcot-Marie-Tooth病，这是一种严重的遗传性运动和感觉神经病。在这项研究中，我们鉴定了一种与MTMR 2特异性相互作用但不与MTM 1相互作用的蛋白质。通过质谱分析显示相互作用的蛋白质是MTMR 5，MTM家族的无催化活性的成员。我们还表明，MTMR 2通过其卷曲螺旋结构域与MTMR 5相互作用，并且MTMR 2或MTMR 5的卷曲螺旋结构域中的突变消除了这种相互作用。通过这种相互作用，MTMR 5增加了MTMR 2的酶活性，并决定了其亚细胞定位。这篇文章展示了一个活跃的MTM成员被一个不活跃的家族成员所调节。
The myotubularin (MTM) family constitutes one of the most highly conserved protein-tyrosine phosphatase subfamilies in eukaryotes. MTM1, the archetypal member of this family, is mutated in X-linked myotubular myopathy, whereas mutations in the MTM-related (MTMR)2 gene cause the type 4B1 Charcot-Marie-Tooth disease, a severe hereditary motor and sensory neuropathy. In this study, we identified a protein that specifically interacts with MTMR2 but not MTM1. The interacting protein was shown by mass spectrometry to be MTMR5, a catalytically inactive member of the MTM family. We also demonstrate that MTMR2 interacts with MTMR5 via its coiled-coil domain and that mutations in the coiled-coil domain of either MTMR2 or MTMR5 abrogate this interaction. Through this interaction, MTMR5 increases the enzymatic activity of MTMR2 and dictates its subcellular localization. This article demonstrates an active MTM member being regulated by an inactive family member.