Kim Youngjun, Gentry Matthew S, Harris Thurl E, Wiley Sandra E, Lawrence John C, Dixon Jack E
Departments of Pharmacology and Cellular and Molecular Medicine, School of Medicine, University of California at San Diego, La Jolla, CA 92093, USA.
Proc Natl Acad Sci U S A. 2007 Apr 17;104(16):6596-601. doi: 10.1073/pnas.0702099104. Epub 2007 Apr 9.
A newly emerging family of phosphatases that are members of the haloacid dehalogenase superfamily contains the catalytic motif DXDX(T/V). A member of this DXDX(T/V) phosphatase family known as Dullard was recently shown to be a potential regulator of neural tube development in Xenopus [Satow R, Chan TC, Asashima M (2002) Biochem Biophys Res Commun 295:85-91]. Herein, we demonstrate that human Dullard and the yeast protein Nem1p perform similar functions in mammalian cells and yeast cells, respectively. In addition to similarity in primary sequence, Dullard and Nem1p possess similar domains and show similar substrate preferences, and both localize to the nuclear envelope. Additionally, we show that human Dullard can rescue the aberrant nuclear envelope morphology of nem1Delta yeast cells, functionally replacing Nem1p. Finally, Nem1p, has been shown to deposphorylate the yeast phosphatidic acid phosphatase Smp2p [Santos-Rosa H, Leung J, Grimsey N, Peak-Chew S, Siniossoglou S (2005) EMBO J 24:1931-1941], and we show that Dullard dephosphorylates the mammalian phospatidic acid phosphatase, lipin. Therefore, we propose that Dullard participates in a unique phosphatase cascade regulating nuclear membrane biogenesis, and that this cascade is conserved from yeast to mammals.
一个新出现的磷酸酶家族属于卤代酸脱卤酶超家族，其包含催化基序DXDX(T/V)。最近发现，这个DXDX(T/V)磷酸酶家族的一个成员Dullard是非洲爪蟾神经管发育的潜在调节因子[佐藤R，陈TC，浅岛M（2002年）《生物化学与生物物理研究通讯》295：85 - 91]。在此，我们证明人Dullard和酵母蛋白Nem1p分别在哺乳动物细胞和酵母细胞中发挥相似功能。除了一级序列相似外，Dullard和Nem1p具有相似的结构域，表现出相似的底物偏好，且都定位于核膜。此外，我们表明人Dullard可以挽救nem1Δ酵母细胞异常的核膜形态，在功能上替代Nem1p。最后，已证明Nem1p可使酵母磷脂酸磷酸酶Smp2p去磷酸化[桑托斯 - 罗萨H，梁J，格里姆西N，皮克 - 丘S，西尼奥索格卢S（2005年）《欧洲分子生物学组织杂志》24：1931 - 1941]，并且我们表明Dullard可使哺乳动物磷脂酸磷酸酶lipin去磷酸化。因此，我们提出Dullard参与一个独特的磷酸酶级联反应来调节核膜生物发生，并且这个级联反应从酵母到哺乳动物都是保守的。
