Fly and mammalian lipid phosphate phosphatase isoforms differ in activity both in vitro and in vivo
Fly and mammalian lipid phosphate phosphatase isoforms differ in activity both in vitro and in vivo
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DOI：
10.1038/sj.embor.embor900
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发表时间：
2003-08-01
期刊：
影响因子：
7.7
通讯作者：
Howard, K
中科院分区：
文献类型：
--
作者：
Burnett, C;Howard, K
Wunen （Wun）是一种脂质磷酸磷酸酶（LPP）的同源物，在果蝇胚胎发生过程中对原始生殖细胞（PGCs）的迁移和存活起着至关重要的作用。过去的研究表明，LPP亚型在某些系统中可能显示出功能冗余，并且它们在体外具有广泛的脂质磷酸酶活性，它们之间几乎没有明显的特异性。我们在这里表明，苍蝇Wun和哺乳动物LPPs之间的生化活性存在显著差异，Wun的活性范围比报道的哺乳动物LPPs要窄。此外，尽管它在体外对一系列底物有活性，但小鼠Lpp1在体内对一种内源性果蝇生殖细胞特异性因子没有活性。相反，人类LPP3是活跃的，导致异常迁移和PGC死亡。这些结果首次在模式生物中显示了LPP亚型之间生物活性的绝对差异，并可能指向果蝇和人类之间保守的潜在信号系统。
Wunen (Wun), a homologue of a lipid phosphate phosphatase (LPP), has a crucial function in the migration and survival of primordial germ cells (PGCs) during Drosophila embryogenesis. Past work has indicated that the LPP isoforms may show functional redundancy in certain systems, and that they have broad-range lipid phosphatase activities in vitro, with little apparent specificity between them. We show here that there are marked differences in biochemical activity between fly Wun and mammalian LPPs, with Wun having a narrower activity range than has been reported for the mammalian LPPs. Furthermore, although it is active on a range of substrates in vitro, mouse Lpp1 has no activity on an endogenous Drosophila germ-cell-specific factor in vivo. Conversely, human LPP3 is active, resulting in aberrant migration and PGC death. These results show an absolute difference in bioactivity among LPP isoforms for the first time in a model organism and may point towards an underlying signalling system that is conserved between flies and humans.