Journal of Biological Chemistry
Volume 279, Issue 37, 10 September 2004, Pages 38590-38596
Journal home page for Journal of Biological Chemistry

Mechanisms of Signal Transduction
A PTEN-like Phosphatase with a Novel Substrate Specificity*

https://doi.org/10.1074/jbc.M404959200Get rights and content
Under a Creative Commons license
open access

We show that a novel PTEN-like phosphatase (PLIP) exhibits a unique preference for phosphatidylinositol 5-phosphate (PI(5)P) as a substrate in vitro. PI(5)P is the least characterized member of the phosphoinositide (PI) family of lipid signaling molecules. Recent studies suggest a role for PI(5)P in a variety of cellular events, such as tumor suppression, and in response to bacterial invasion. Determining the means by which PI(5)P levels are regulated is therefore key to understanding these cellular processes. PLIP is highly enriched in testis tissue and, similar to other PI phosphatases, exhibits poor activity against several proteinaceous substrates. Despite a recent report suggesting a role for PI(5)P in the regulation of Akt, the overexpression of wild-type or catalytically inactive PLIP in Chinese hamster ovary-insulin receptor cells or a dsRNA-mediated knockdown of PLIP mRNA levels in Drosophila S2 cells does not alter Akt activity or phosphorylation. The unique in vitro catalytic activity and detailed biochemical and kinetic analyses reported here will be of great value in our continued efforts to identify in vivo substrate(s) for this highly conserved phosphatase.

Cited by (0)

*

This work was supported by National Institutes of Health Grant 18024 and funds from the Walther Cancer Institute (to J. E. D.) and by National Institutes of Health Pharmacology Training Grant NIH 2 T32 GM07752-25 (to D. J. P.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The nucleotide sequence(s) reported in this paper has been submitted to the DDBJ/GenBank/EBI Data Bank with accession number(s) TPA: BK005540.