Wu Y, Dowbenko D, Pisabarro M T, Dillard-Telm L, Koeppen H, Lasky L A
Department of Molecular Oncology, Genentech, Inc., South San Francisco, California 94080, USA.
J Biol Chem. 2001 Jun 15;276(24):21745-53. doi: 10.1074/jbc.M101480200. Epub 2001 Mar 2.
The tumor suppressor PTEN is a phosphatidylinositol phospholipid phosphatase, which indirectly down-regulates the activity of the protein kinase B/Akt survival kinases. Examination of sequence data bases revealed the existence of a highly conserved homologue of PTEN. This homologue, termed PTEN 2, contained an extended amino-terminal domain having four potential transmembrane motifs, a lipid phosphatase domain, and a potential lipid-binding C2 domain. Transcript analysis demonstrated that PTEN 2 is expressed only in testis and specifically in secondary spermatocytes. In contrast to PTEN, PTEN 2 was localized to the Golgi apparatus via the amino-terminal membrane-spanning regions. Molecular modeling suggested that PTEN 2 is a phospholipid phosphatase with potential specificity for the phosphate at the 3 position of inositol phosphates. Enzymatic analysis of PTEN 2 revealed substrate specificity that is similar to PTEN, with a preference for the dephosphorylation of the phosphatidylinositol 3,5-phosphate phospholipid, a known mediator of vesicular trafficking. Together, these data suggest that PTEN 2 is a Golgi-localized, testis-specific phospholipid phosphatase, which may contribute to the terminal stages of spermatocyte differentiation.
肿瘤抑制因子PTEN是一种磷脂酰肌醇磷脂磷酸酶，它间接下调蛋白激酶B/Akt存活激酶的活性。对序列数据库的检查揭示了PTEN存在一个高度保守的同源物。这个同源物被称为PTEN 2，它包含一个延长的氨基末端结构域，该结构域有四个潜在的跨膜基序、一个脂质磷酸酶结构域和一个潜在的脂质结合C2结构域。转录分析表明，PTEN 2仅在睾丸中表达，且特异性地表达于次级精母细胞中。与PTEN不同，PTEN 2通过氨基末端跨膜区域定位于高尔基体。分子建模表明，PTEN 2是一种对肌醇磷酸3位的磷酸具有潜在特异性的磷脂磷酸酶。对PTEN 2的酶学分析揭示了其与PTEN相似的底物特异性，更倾向于使磷脂酰肌醇3,5-磷酸磷脂去磷酸化，磷脂酰肌醇3,5-磷酸磷脂是一种已知的囊泡运输介质。总之，这些数据表明PTEN 2是一种定位于高尔基体、睾丸特异性的磷脂磷酸酶，可能有助于精母细胞分化的终末阶段。
