Nedachi Taku, Conti Marco
Division of Reproductive Biology, Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Development. 2004 Oct;131(20):4987-98. doi: 10.1242/dev.01368. Epub 2004 Sep 15.
Protein tyrosine phosphatase nonreceptor type 13 (PTPN13) is a tyrosine phosphatase with multiple interacting domains that has been implicated previously in the regulation of apoptosis. We provide evidence that PTPN13 plays an important role in the control of the meiotic cell cycle. A cDNA coding for PTPN13 was isolated during the screening for the substrate of protein kinase A expressed in mammalian oocytes. PTPN13 is expressed in both mouse and Xenopus oocytes and is a substrate for protein kinase A in vitro and in vivo. Expression of a truncated constitutively-active PTPN13 in Xenopus oocytes synergizes with progesterone in the induction of germinal vesicle breakdown, the translation of Mos, the phosphorylation of Erk and the dephosphorylation of Cdc2. The phosphatase activity of PTPN13 is required for this synergism. Oocyte injection with specific small interference RNA downregulates the expression of mRNA for PTPN13 and blocks oocyte maturation induced by progesterone, a blockade that can be overcome by Cdc25 overexpression. These findings indicate that PTPN13 is involved in the regulation of the meiotic cell cycle.
蛋白酪氨酸磷酸酶非受体13型(PTPN13)是一种具有多个相互作用结构域的酪氨酸磷酸酶,此前已被证明与细胞凋亡调控有关。我们提供的证据表明,PTPN13在减数分裂细胞周期的控制中发挥重要作用。在筛选哺乳动物卵母细胞中表达的蛋白激酶A底物的过程中,分离出了编码PTPN13的cDNA。PTPN13在小鼠和非洲爪蟾卵母细胞中均有表达,并且在体外和体内都是蛋白激酶A的底物。在非洲爪蟾卵母细胞中表达截短的组成型活性PTPN13,可与孕酮协同诱导生发泡破裂、Mos的翻译、Erk的磷酸化以及Cdc2的去磷酸化。这种协同作用需要PTPN13的磷酸酶活性。向卵母细胞注射特异性小干扰RNA可下调PTPN13的mRNA表达,并阻断孕酮诱导的卵母细胞成熟,而过表达Cdc25可克服这种阻断。这些发现表明,PTPN13参与减数分裂细胞周期的调控。