A PTEN-related 5-Phosphatidylinositol Phosphatase Localized in the Golgi

Merlot, Sylvain; Meili, Ruedi; Pagliarini, David J.; Maehama, Tomohiko; Dixon, Jack E.; Firtel, Richard A.

doi:10.1074/jbc.m306318200

Cited by 34 publications

(28 citation statements)

References 56 publications

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“…A TLC analysis of the reaction products, shown in Fig. 2A, revealed that PLIP exhibits a highly selective substrate specificity for PI(5)P. This substrate preference is shared by the Dictyostelium ortholog of PLIP (30). As expected, the mutation of the predicted catalytic cysteine residue to serine (C132S) nullified this activity.…”

Section: Identification Of Plip As a Pten-likementioning

confidence: 94%

A PTEN-like Phosphatase with a Novel Substrate Specificity

Pagliarini

Worby

Dixon

2004

Journal of Biological Chemistry

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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.Protein-tyrosine phosphatases (PTPs) 1 are a family of ϳ100 phosphatases characterized by their highly conserved CX 5 R catalytic motif. Once thought to dephosphorylate only phosphotyrosine residues, a subset of PTPs are now known to dephosphorylate phosphoserine-and phosphothreonine-containing proteins, as well as to use RNA and phosphoinositides as substrates in vitro and in vivo (1-5). A structural study of the tumor suppressor phosphatase PTEN revealed a wider active site cleft and suggested positions of key basic amino acids in the P-loop (CKAGKGR) among the reasons for its ability to use the phosphoinositide PI(3,4,5)P 3 as its preferred substrate (6). Consistent with this observation, other PTPs possessing highly similar or identical active site motifs, including the PTEN homologs PTEN 2 and TPIP, bacterial effector phosphatases SopB and IpgD, and inositol polyphosphate-4 phosphatases 1 and 2, have also now been shown to possess activity against phosphoinositide substrates (7-13) (see Fig. 1A).In our bioinformatic searches of the NCBI databases for other PTEN-like PTPs, we identified a highly conserved phosphatase with over 60 orthologs throughout the Animalia, Plantae, Protista, and Eubacteria kingdoms. Here, we report that the murine ortholog of this PTEN-like phosphatase (PLIP), 2 possesses an in vitro activity against a rare phosphoinositide, PI(5)P.Phosphatidylinositol, an abundant membrane phospholipid, is capable of being phosphorylated on the 3, 4, and 5 positions of its inositol ring to form seven unique lipid signaling molecules collectively termed phosphoinositides (PIs) (14). PIs regulate critical cellular functions, including apoptosis, membrane trafficking, cytoskeletal rearrangement, metabolism, growth, and differentiation by altering the subcellular location, state of aggregation, and activity of a variety of cellular en...

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Section: Identification Of Plip As a Pten-likementioning

confidence: 94%

A PTEN-like Phosphatase with a Novel Substrate Specificity

Pagliarini

Worby

Dixon

2004

Journal of Biological Chemistry

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“…A phosphatase with a highly specific 5-phosphatase activity towards PtdIns5P in vitro has been described in mammals (Merlot et al 2003;Pagliarini et al 2004). This enzyme, originally named phospholipid-inositol phosphatase and later renamed PTPMT1 (Blero et al 2007), can potentially convert PtdIns5P to PtdIns but whether this enzyme has a role in reducing the levels of PtdIns5P in vivo is not clear.…”

Section: Phosphatasesmentioning

confidence: 97%

An Introduction to Phosphoinositides

Maffucci¹

2012

Phosphoinositides and Disease

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Phosphoinositides (PIs) are minor components of cellular membranes that play critical regulatory roles in several intracellular functions. This chapter describes the main enzymes regulating the turnover of each of the seven PIs in mammalian cells and introduces to some of their intracellular functions and to some evidences of their involvement in human diseases. Due to the complex interrelation between the distinct PIs and the plethora of functions that they can regulate inside a cell, this chapter is not meant to be a comprehensive coverage of all aspects of PI signalling but rather an introduction to this complex signalling field. For more details of their regulation/functions and extensive description of their intracellular roles, more detailed reviews are suggested on each single topic.

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“…This phosphatase harbours a transmembrane domain in its N terminus. It has only a weak overall similarity to PTEN and, in contrast to the 3-phosphatase activity of PTEN, has a highly specific 5-phosphatase activity against PtdIns5P in vitro [79]. PLIP is unrelated to the inositol polyphosphate 5-phosphatase family ( Fig.…”

Section: Phospholipid-inositol Phosphatase (Plip)mentioning

confidence: 99%

“…A search in a Dictyostelium sequence data base for additional PTEN homologs revealed the existence of a new family of phosphatases with orthologs in eukaryotes Bipolar disorder [122] Lethal (−/−) [23] and prokaryotes [79,97]. In mammals, a similar PTEN-like phosphatase, initially called phospholipid-inositol phosphatase (PLIP), has been described.…”

Section: Phospholipid-inositol Phosphatase (Plip)mentioning

confidence: 99%

Phosphoinositide phosphatases in a network of signalling reactions

Bléro

Payrastre

Schurmans

et al. 2007

Pflugers Arch - Eur J Physiol

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Phosphoinositide phosphatases dephosphorylate the three positions (D-3, 4 and 5) of the inositol ring of the poly-phosphoinositides. They belong to different families of enzymes. The PtdIns(3,4)P(2) 4-phosphatase family, the tumour suppressor phosphatase and tensin homolog deleted on chromosome 10 (PTEN), SAC1 domain phosphatases and myotubularins belong to the tyrosine protein phosphatases superfamily. They share the presence of a conserved cysteine residue in the consensus CX(5)RT/S. Another family consists of the inositol polyphosphate 5-phosphatase isoenzymes. The importance of these phosphoinositide phosphatases in cell regulation is illustrated by multiple examples of their implications in human diseases such as Lowe syndrome, X-linked myotubular myopathy, cancer, diabetes or bacterial infection.

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A PTEN-related 5-Phosphatidylinositol Phosphatase Localized in the Golgi

Cited by 34 publications

References 56 publications

A PTEN-like Phosphatase with a Novel Substrate Specificity

A PTEN-like Phosphatase with a Novel Substrate Specificity

An Introduction to Phosphoinositides

Phosphoinositide phosphatases in a network of signalling reactions

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