PTEN 2, a Golgi-associated Testis-specific Homologue of the PTEN Tumor Suppressor Lipid Phosphatase

doi:10.1074/jbc.M101480200

PTEN 2, a Golgi-associated Testis-specific Homologue of the PTEN Tumor Suppressor Lipid Phosphatase*

From the Departments of ^‡Molecular Oncology,^§Protein Engineering, and ^¶Pathology, Genentech, Inc., South San Francisco, California 94080

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.

Footnotes

↵* The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
↵‖ To whom correspondence should be addressed: Dept. of Molecular Oncology, Genentech, Inc., 460 Pt. San Bruno Blvd., South San Francisco, CA 94080. Tel.: 650-225-1123; Fax: 650-225-6127; E-mail: lal@gene.com.
Published, JBC Papers in Press, March 2, 2001, DOI 10.1074/jbc.M101480200
↵2 T. Wu, personal communication.
Abbreviations:

PI3K

phosphatidylinositol 3-kinase

PKB

protein kinase B

PIP₃

phosphatidylinositol 3-phosphate phospholipid

PIP₃

4, phosphatidylinositol 3,4-phosphate phospholipid

PIP₃

4,5, phosphatidylinositol 3,4,5-phosphate phospholipid

MAGUK

membrane-associated guanylate kinase

GST

glutathioneS-transferase

GFP

green fluorescence protein

kb

kilobase(s)

bp

base pair(s)

DTT

dithiothreitol

PDZ

PSD95, discs large, Z01 domain

PTEN

phosphatase with tensin homology.
- Received February 15, 2001.
- Revision received March 1, 2001.
The American Society for Biochemistry and Molecular Biology, Inc.