Three mammalian lipins act as phosphatidate phosphatases with distinct tissue expression patterns
Three mammalian lipins act as phosphatidate phosphatases with distinct tissue expression patterns
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DOI：
10.1074/jbc.m610745200
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发表时间：
2007-02-09
影响因子：
4.8
通讯作者：
Reue, Karen
中科院分区：
文献类型：
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作者：
Donkor, Jimmy;Sariahmetoglu, Meltem;Reue, Karen
我们以前确定的Lpin 1基因，编码脂蛋白-1突变，作为脂肪肝营养不良（fld）突变小鼠脂肪营养不良的根本原因。Lipin-1通常在脂肪组织和骨骼肌中高水平表达，在fld小鼠中缺乏lipin-1会导致脂肪组织发育受损、胰岛素抵抗和能量消耗改变。我们还确定了另外两个功能未知的脂蛋白家族成员，脂蛋白-2和脂蛋白-3。Han等人（Han，G.美国，吴，W.一、和卡曼，G. M.（2006）J.Biol.Chem.281，9210 -9218）最近证明，酵母中的单一脂蛋白同系物Smp 2表现出1型磷脂酸磷酸酶（PAP 1）活性，其在甘油脂合成中具有关键作用。在这里，我们证明，脂蛋白-1占所有的PAPI活动在白色和棕色脂肪组织和骨骼肌。然而，Lipin-1缺陷小鼠的肝脏表现出正常的PAP 1活性，表明Lipin蛋白家族的其他成员可能具有PAPI活性。与这种可能性一致，重组脂蛋白-2和脂蛋白-3具有PAPI活性。三个脂蛋白家族成员中的每一个都显示出在所采用的条件下对磷脂酸具有特异性的Mg 2+依赖性活性。不同的脂蛋白表现出不同的组织表达模式。我们的研究结果建立了三种哺乳动物的lipin蛋白作为PAP I酶，并解释了lipin-1缺陷型fld小鼠脂肪营养不良的生化基础。
We previously identified mutations in the Lpin1 gene, encoding lipin-1, as the underlying cause of lipodystrophy in the fatty liver dystrophy (fld) mutant mouse. Lipin-1 is normally expressed at high levels in adipose tissue and skeletal muscle, and deficiency in the fld mouse causes impaired adipose tissue development, insulin resistance, and altered energy expenditure. We also identified two additional lipin protein family members of unknown function, lipin-2 and lipin-3. Han et al. (Han, G. S., Wu, W. I., and Carman, G. M. (2006) J. Biol. Chem. 281,9210-9218) recently demonstrated that the single lipin homolog in yeast, Smp2, exhibits phosphatidate phosphatase type-1 (PAP1) activity, which has a key role in glycerolipid synthesis. Here we demonstrate that lipin-1 accounts for all of the PAPI activity in white and brown adipose tissue and skeletal muscle. However, livers of lipin-1-deficient mice exhibited normal PAP1 activity, indicating that other members of the lipin protein family could have PAPI activity. Consistent with this possibility, recombinant lipin-2 and lipin-3 possess PAPI activity. Each of the three lipin family members showed Mg2+-dependent activity that was specific for phosphatidate under the conditions employed. The different lipins showed distinct tissue expression patterns. Our results establish the three mammalian lipin proteins as PAP I enzymes and explain the biochemical basis for lipodystrophy in the lipin-1-deficient fld mouse.