PTEN 2, a Golgi-associated testis-specific homologue of the PTEN tumor suppressor lipid phosphatase
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Published on: August 13, 2017
Y Wu1, D Dowbenko, M T Pisabarro
1Department of Molecular Oncology, Genentech, Inc., South San Francisco, California 94080, USA.
Abstract:
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.
Insights
Researchers discovered PTEN 2, a novel testis-specific protein phosphatase. This protein, localized to the Golgi apparatus, may play a role in spermatocyte differentiation.
Area of Science:
- Biochemistry
- Molecular Biology
- Cell Biology
Background:
- The tumor suppressor PTEN is a phosphatidylinositol phospholipid phosphatase that regulates protein kinase B/Akt signaling.
- PTEN indirectly down-regulates the activity of Akt survival kinases.
Purpose of the Study:
- To identify and characterize a novel homologue of PTEN.
- To investigate the function and localization of the PTEN homologue, termed PTEN 2.
Main Methods:
- Sequence database analysis to identify PTEN homologues.
- Transcript analysis to determine PTEN 2 expression patterns.
- Molecular modeling to predict PTEN 2 structure and function.
- Enzymatic assays to determine PTEN 2 substrate specificity.
Main Results:
- A highly conserved PTEN homologue, PTEN 2, was identified with unique features including transmembrane domains.
- PTEN 2 is specifically expressed in the testis, localized to secondary spermatocytes and the Golgi apparatus.
- PTEN 2 functions as a phospholipid phosphatase, with substrate specificity similar to PTEN, preferring phosphatidylinositol 3,5-phosphate.
- PTEN 2's localization and enzymatic activity suggest a role in vesicular trafficking.
Conclusions:
- PTEN 2 is a testis-specific, Golgi-localized phospholipid phosphatase.
- PTEN 2 may be involved in regulating vesicular trafficking during spermatocyte differentiation.
- PTEN 2 represents a novel player in male reproductive biology.
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