Cloning and characterization of two human isozymes of Mg2+-independent phosphatidic acid phosphatase
Cloning and characterization of two human isozymes of Mg2+-independent phosphatidic acid phosphatase
复制标题
DOI：
10.1074/jbc.272.39.24572
复制
发表时间：
1997-09-26
影响因子：
4.8
通讯作者：
Kanoh, H
中科院分区：
文献类型：
--
作者：
Kai, M;Wada, I;Kanoh, H
我们获得了两个编码人磷酸磷脂酸磷酸酶（PAP）同工酶的cDNA克隆，分别命名为PAP-2a（M-r = 32，158）和PAP-2b（M-r = 35，119），这两个同工酶都含有6个跨膜结构域。PAP-Za和PAP-2b的同源性分别为47%和83%，分别与小鼠35-kDa PAP和大鼠Dri 42蛋白的同源性为94%，与果蝇Wunen蛋白的同源性为34-39%。鉴于Wunen和Dri 42分别在生殖细胞迁移和上皮分化中的功能，这些发现出乎意料地表明PAP同种型在细胞生长和分化中的关键作用，尽管这两种PAP水解溶血磷脂酸和神经酰胺-1-磷酸。除了磷脂酸，仅检测到PAP-2b的鞘氨醇-1-磷酸水解，PAP-2b在所有检测的人体组织中几乎普遍表达，而PAP-2a的表达相对可变，在胎盘和胸腺中极低。在HeLa细胞中，PAP-2a的转录不受不同刺激的影响，而PAP-2b被表皮生长因子诱导（高达3倍）。这些研究结果表明，尽管结构相似，两个PAP同工酶可能发挥不同的功能，通过其不同的模式的底物利用和转录调控。
We obtained two human cDNA clones encoding phosphatidic acid phosphatase (PAP) isozymes named PAP-2a (M-r = 32,158) and -2b (M-r = 35, 119), both of which contained six putative transmembrane domains, Both enzymes were glycosylated and cleaved by N glycanase and endo-beta-galactosidase, thus suggesting their post-Golgi localization. PAP-Za and -2b shared 47% identical sequence and were judged to be the human counterparts of the previously sequenced mouse 35-kDa PAP(83% identity) and rat Dri42 protein (94% identity), respectively, Furthermore, the sequences of both PAPs were 34-39% identical to that of Drosophila Wunen protein. In view of the functions ascribed to Wunen and Dri42 in germ cell migration and epithelial differentiation, respectively, these findings unexpectedly suggest critical roles of PAP isoforms in cell growth and differentiation, Although the two PAPs hydrolyzed lysophosphatidate and ceramide-l-phosphate. in addition to phosphatidate, the hydrolysis of sphingosine-l-phosphate was detected only for PAP-2b, PAP-2b was expressed almost ubiquitously in all human tissues examined, whereas the expression of PAP-2a was relatively variable, being extremely low in the placenta and thymus, In HeLa cells, the transcription of PAP-2a was not affected by different stimuli, whereas PAP-2b was induced (up to 3-fold) by epidermal growth factor. These findings indicate that despite structural similarities, the two PAP isozymes may play distinct functions through their different patterns of substrate utilization and transcriptional regulation.