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PMID:9811831

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Citation

Myers, MP, Pass, I, Batty, IH, Van der Kaay, J, Stolarov, JP, Hemmings, BA, Wigler, MH, Downes, CP and Tonks, NK (1998) The lipid phosphatase activity of PTEN is critical for its tumor supressor function. Proc. Natl. Acad. Sci. U.S.A. 95:13513-8

Abstract

Since their discovery, protein tyrosine phosphatases have been speculated to play a role in tumor suppression because of their ability to antagonize the growth-promoting protein tyrosine kinases. Recently, a tumor suppressor from human chromosome 10q23, called PTEN or MMAC1, has been identified that shares homology with the protein tyrosine phosphatase family. Germ-line mutations in PTEN give rise to several related neoplastic disorders, including Cowden disease. A key step in understanding the function of PTEN as a tumor suppressor is to identify its physiological substrates. Here we report that a missense mutation in PTEN, PTEN-G129E, which is observed in two Cowden disease kindreds, specifically ablates the ability of PTEN to recognize inositol phospholipids as a substrate, suggesting that loss of the lipid phosphatase activity is responsible for the etiology of the disease. Furthermore, expression of wild-type or substrate-trapping forms of PTEN in HEK293 cells altered the levels of the phospholipid products of phosphatidylinositol 3-kinase and ectopic expression of the phosphatase in PTEN-deficient tumor cell lines resulted in the inhibition of protein kinase (PK) B/Akt and regulation of cell survival.

Links

PubMed PMC24850

Keywords

Cell Line; Escherichia coli; Genes, Tumor Suppressor; Germ-Line Mutation; Humans; PTEN Phosphohydrolase; Phosphoric Monoester Hydrolases/chemistry; Phosphoric Monoester Hydrolases/genetics; Phosphoric Monoester Hydrolases/metabolism; Protein Tyrosine Phosphatases; Tumor Suppressor Proteins

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:PTEN

enables

GO:0004438: phosphatidylinositol-3-phosphatase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:PTEN

enables

GO:0016314: phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:PTEN

involved_in

GO:0046856: phosphatidylinositol dephosphorylation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:PTEN

enables

GO:0051800: phosphatidylinositol-3,4-bisphosphate 3-phosphatase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete


See also

References

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