PTEN 2, a Golgi-associated testis-specific homologue or the PTEN tumor suppressor lipid phosphatase

The tumor suppressor PTEN is a phosphatidylinositol phospholipid phosphatas e, which indirectly down-regulates the activity of the protein kinase B/Akt survival kinases. Examination of sequence data bases revealed the existenc e of a highly conserved homologue of PTEN, This homologue, termed PTEN 2, c ontained an extended amino-terminal domain having four potential transmembr ane motifs, a lipid phosphatase domain, and a potential lipid-binding C2 do main. Transcript analysis demonstrated that PTEN 2 is expressed only in tes tis and specifically in secondary spermatocytes, In contrast to PTEN, PTEN 2 was localized to the Golgi apparatus via the amino-terminal membrane-span ning regions. Molecular modeling suggested that PTEN 2 is a phospholipid ph osphatase with potential specificity for the phosphate at the 3 position of inositol phosphates, Enzymatic analysis of PTEN 2 revealed substrate speci ficity that is similar to PTEN, with a preference for the dephosphorylation of the phosphatidylinositol 3,5-phosphate phospholipid, a known mediator o f vesicular trafficking. Together, these data suggest that PTEN 2 is a Golg i-localized, testis-specific phospholipid phosphatase, which may contribute to the terminal stages of spermatocyte differentiation.