Molecular mechanisms of the PRL phosphatases

Ríos, Pablo; Li, Xun; Köhn, Maja

doi:10.1111/j.1742-4658.2012.08565.x

Cited by 109 publications

(166 citation statements)

References 120 publications

(333 reference statements)

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“…We noticed the presence of a weak signal at a slightly lower molecular weight than PRL1, which similarly disappeared after H 2 O 2 stimulation. We speculated that this signal represents endogenous PRL2 because the molecular mass of PRL2 is slightly smaller than that of PRL1 (2). Indeed, the mobility of ectopically expressed PRL2 (without any tags) was identical to the detected signal (Fig.…”

Section: Sensitive Oxidation Of Prl By H 2 O 2 -mentioning

confidence: 66%

“…The PRL 2 family is a unique subfamily of protein-tyrosine phosphatases; it consists of three homologous members (PRL1-PRL3), which have a high degree (Ͼ75%) of amino acid sequence identity. PRLs are the only protein-tyrosine phosphatases known to have a C-terminal CAAX motif, which anchors PRLs to the plasma membrane by prenylation (1).…”

mentioning

confidence: 99%

“…PRLs are the only protein-tyrosine phosphatases known to have a C-terminal CAAX motif, which anchors PRLs to the plasma membrane by prenylation (1). By exhaustive gene expression profiling of human colorectal cancers, PRL3 was identified as the only gene overexpressed in all metastases but not in primary tumors or normal epithelia (2). Indeed, it has been reported that overexpression of PRLs, especially of PRL3, frequently occurs in various types of metastatic human cancers and is associated with patient mortality (3).…”

mentioning

confidence: 99%

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Thioredoxin-related Protein 32 (TRP32) Specifically Reduces Oxidized Phosphatase of Regenerating Liver (PRL)

Ishii

Funato

Miki

2013

Journal of Biological Chemistry

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Background: Phosphatase of regenerating liver (PRL) is a metastasis-associated protein that is susceptible to inactivation by oxidation. Results: Thioredoxin-related protein 32 (TRP32) specifically binds and reduces oxidized PRL. Conclusion:The redox state of PRL is regulated by this specific member of the thioredoxin (TRX) family proteins. Significance: TRP32 may be the key regulator of PRL function and contribute to cancer metastasis.

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Section: Sensitive Oxidation Of Prl By H 2 O 2 -mentioning

confidence: 66%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Thioredoxin-related Protein 32 (TRP32) Specifically Reduces Oxidized Phosphatase of Regenerating Liver (PRL)

Ishii

Funato

Miki

2013

Journal of Biological Chemistry

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“…To date, biochemical analyses using cultured cells have suggested that PRL can affect several signaling pathways involved in the regulation of cell proliferation, including mammalian/mechanistic target of rapamycin (mTOR) (7,8).…”

Section: Introductionmentioning

confidence: 99%

Membrane protein CNNM4–dependent Mg2+ efflux suppresses tumor progression

Funato¹,

Mizukami²,

Du³

et al. 2014

J. Clin. Invest.

195

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“…First, we characterize the biochemical activity of this Leishmania phosphatase, which we named LmPRL-1 due to its similarity to the family of mammalian phosphatases of the regenerating liver (PRLs). PRLs are thought to participate in the control of various cellular processes, such as proliferation, differentiation, and motility (42). Second, we provide evidence that the LmPRL-1 phosphatase can be secreted during infection of macrophages and that it contributes to the survival of the parasite in these host cells.…”

mentioning

confidence: 85%

Characterization of the Protein Tyrosine Phosphatase LmPRL-1 Secreted by Leishmania major via the Exosome Pathway

et al. 2017

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Similar to other intracellular pathogens, Leishmania parasites are known to evade the antimicrobial effector functions of host immune cells. To date, however, only a few virulence factors have been described for Leishmania major, one of the causative agents of cutaneous leishmaniasis. Here, we have characterized the expression and function of an L. major phosphatase, which we termed LmPRL-1. This enzyme shows a strong structural similarity to the human phosphatases of regenerating liver (PRL-1, -2, and -3) that regulate the proliferation, differentiation, and motility of cells. The biochemical characterization of the L. major phosphatase revealed that the enzyme is redox sensitive. When analyzing the subcellular localization of LmPRL-1 in promastigotes, amastigotes, and infected macrophages, we found that the phosphatase was predominantly expressed and secreted by promastigotes via the exosome route. Finally, we observed that ectopic expression of LmPRL-1 in L. major led to an increased number of parasites in macrophages. From these data, we conclude that the L. major phosphatase LmPRL-1 contributes to the intracellular survival of the parasites in macrophages.KEYWORDS Leishmania, exosome, macrophage, tyrosine phosphatase L eishmaniasis is an infectious disease prevalent worldwide that is caused by kinetoplastid protozoan parasites belonging to the genus Leishmania (1). In nature, this heteroxenous parasite is transmitted by the bites of sand flies. Following the inoculation of flagellated promastigotes into the dermis of the host, the parasites are rapidly endocytosed by phagocytic cells, in which they differentiate into amastigotes, multiply, and reach inner compartments and organs, such as draining lymph nodes, spleen, liver, and bone marrow. The life cycle of the parasite is completed after ingestion of amastigote-infected cells by sand flies during their blood meal. In the digestive tract of their vector, parasites transform back into extracellular promastigotes that develop into infectious metacyclics (2). Depending on the status of the host immune system and the Leishmania species, the infection of mammals leads either to mostly self-healing skin lesions (cutaneous leishmaniasis [CL]) or to a systemic disease, termed visceral leishmaniasis (VL) or kala-azar, that is lethal if untreated (3-5).To survive in their hosts, Leishmania parasites need to quickly adapt their growth, metabolism, and mechanisms of protection to their new environment. Interestingly, only a few genes are differentially expressed during this adaptive process, suggesting an important role for the regulation of protein translation (6). Leishmania speciesspecific gene diversity also participates in the adaptation of the parasite to its organ-

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Molecular mechanisms of the PRL phosphatases

Cited by 109 publications

References 120 publications

Thioredoxin-related Protein 32 (TRP32) Specifically Reduces Oxidized Phosphatase of Regenerating Liver (PRL)

Thioredoxin-related Protein 32 (TRP32) Specifically Reduces Oxidized Phosphatase of Regenerating Liver (PRL)

Membrane protein CNNM4–dependent Mg2+ efflux suppresses tumor progression

Characterization of the Protein Tyrosine Phosphatase LmPRL-1 Secreted by Leishmania major via the Exosome Pathway

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