Leishmania mexicana promastigotes secrete a protein tyrosine phosphatase

Escalona‐Montaño, Alma Reyna; Pardavé-Alejandre, Daniel; Cervantes-Sarabia, Rocely; Garcı́a-López, Patricia; Gutiérrez-Quiroz, Manuel; Gutiérrez‐Kobeh, Laila; Becker-Fauser, Ingeborg; Aguirre-Garcı́a, Marı́a Magdalena

doi:10.1007/s00436-010-1863-5

Cited by 8 publications

(16 citation statements)

References 41 publications

(46 reference statements)

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“…The surface‐bound acid phosphatases were further divided into three distinct groups according to molecular weight, resistance to sodium tartrate, and substrate affinity (Remaley et al ., ). In addition to those activities described as either intracellular or membrane‐bound, various studies regarding Leishmania described an intense acidic phosphatase activity in the culture medium (Gottlieb & Dwyer, ; Lovelace & Gottlieb, ; Doyle & Dwyer, ; Shakarian & Dwyer, ; Escalona‐Montaño et al ., ). Recent studies have shown that promastigotes and amastigotes of different pathogenic species secrete sAcP via an unconventional mechanism that involves the release of exosome‐like vesicles; however, the possibility that the enzymes are released via a shedding mechanism cannot be ignored (Silverman et al ., ).…”

Section: Discussionmentioning

confidence: 97%

“…Trypanosomatids, such as Trypanosoma and Leishmania , have the ability to hydrolyze organophosphates; this reaction is catalyzed by different protein phosphatases that are classified either as ecto‐/extracytoplasmic and found on the cell surface or as secreted/extracellular isolated from the culture media (Escalona‐Montaño et al ., ; Szoor, ; Cosentino‐Gomes & Meyer‐Fernandes, ; Gomes et al ., ). Both protein phosphorylation and dephosphorylation are important post‐translational modifications for all known eukaryotic organisms.…”

Section: Introductionmentioning

confidence: 99%

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Different secreted phosphatase activities inLeishmania amazonensis

Fernandes

Soares

Saraiva

et al. 2013

FEMS Microbiol Lett

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Leishmania has strong acid phosphatase activity on the external surface of the plasma membrane and secreted into the extracellular milieu. Secreted acid phosphatase (sAcP), which is the most abundant secreted protein of Leishmania, is also a virulence factor that plays a role in vertebrate infection and survival in sand flies. In this study, we characterized the secreted phosphatase activities in Leishmania amazonensis. Both acidic and alkaline secreted phosphatase activities were observed with β-glycerophosphate and p-nitrophenyl phosphate (p-NPP) hydrolysis and were inhibited with sodium tartrate and sodium orthovanadate. Cytochemical labeling revealed a significant difference in the localization of the electron-dense precipitates depending on the substrate. β-Glycerophosphate electron-dense precipitates were concentrated on both the cell surface and flagellar pocket, whereas p-NPP labeling occurred primarily within intracellular organelles. Orthovanadate-treated metacyclic promastigotes were less infective and were confined to a tight parasitophorous vacuole (PV), which is not characteristic of this Leishmania species. Based on the results, we characterized the presence of different secreted phosphatase activities in L. amazonensis, the influence of the substrate in cytochemical labeling, and the potential involvement of secreted phosphatase activity in both PV maturation and amastigote survival.

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Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Different secreted phosphatase activities inLeishmania amazonensis

Fernandes

Soares

Saraiva

et al. 2013

FEMS Microbiol Lett

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“…The data on inhibition of this PTP are incomplete, 200 µM sodium orthovanadate decreases the L. mexicana PTP activity by 64%, 200 µM ammonium molybdate leads to the 66% inhibition, and 50 µM pervanadate resulted in 61% inhibition of the L. mexicana PTP activity. As expected, PTP activity of this enzyme is resistant to 5 nM calyculin and 1 µM okadaic acid [172].…”

Section: Inmentioning

confidence: 81%

“…Leishmania mexicana is capable to secrete PTP of apparent M w 50 kDa [172], though this enzyme is still only poorly characterized. It is secreted by L. mexicana promastigotes, and may be inhibited (at least in part) by the PTP, but not PP inhibitors.…”

Section: Inmentioning

confidence: 99%

Finding the Smoking Gun: Protein Tyrosine Phosphatases as Tools and Targets of Unicellular Microorganisms and Viruses

Heneberg

2012

CMC

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Protein tyrosine phosphatases (PTPs) are increasingly recognized as important effectors of host-pathogen interactions. Since Guan and Dixon reported in 1990 that phosphatase YopH serves as an essential virulence determinant of Yersinia, the field shifted significantly forward, and dozens of PTPs were identified in various microorganisms and even in viruses. The discovery of extensive tyrosine signaling networks in non-metazoan organisms refuted the moth-eaten paradigm claiming that these organisms rely exclusively on phosphoserine/phosphothreonine signaling. Similarly to humans, phosphotyrosine signaling is thought to comprise a small fraction of total protein phosphorylation, but plays a disproportionately important role in cell-cycle control, differentiation, and invasiveness. Here we summarize the state-of-art knowledge on PTPs of important non-metazoan pathogens (Listeria monocytogenes, Staphylococcus aureus, Porphyromonas gingivalis, Caulobacter crescentus, Yersinia, Synechocystis, Leishmania, Plasmodium falciparum, Entamoeba histolytica, etc.), and focus also at the microbial proteins affecting directly or indirectly the PTPs of the host (Mycobacterium tuberculosis MTSA-10, Bacillus anthracis anthrax toxin, streptococcal β protein, Helicobacter pylori CagA and VacA, Leishmania GP63 and EF-1α, Plasmodium hemozoin, etc.). This is the first review summarizing the knowledge on biological activity and pharmacological inhibition of non-metazoan PTPs, with the emphasis of those important in host-pathogen interactions. Targeting of numerous non-metazoan PTPs is simplified by the fact that they act either as ectophosphatases or are secreted outside of the pathogen. Interfering with tyrosine phosphorylation represents a powerful pharmacologic approach, and even though the PTP inhibitors are difficult to develop, lifting the fog of phosphatase inhibition is of the great market potential and further clinical impact.

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“…The occurrence of secreted phosphatase activity was also described in Leishmania , such as L. tropica (Jaffe et al 1990 ), L. mexicana (Menz et al 1991 ) L. donovani (Gottilieb and Dwyer 1982 ) and L. amazonensis (Martiny et al 1996 ). Recently, a study involving the use of two antibodies and specifi c inhibitors showed that L. mexicana secreted phosphotyrosine phosphatases (Escalona-Montaño et al 2010 ).…”

Section: Identifi Cation and Localization Of Membrane-bound Or Secretmentioning

confidence: 99%

Ecto-nucleotidases and Ecto-phosphatases from Leishmania and Trypanosoma Parasites

Freitas-Mesquita

Meyer‐Fernandes

2013

Subcellular Biochemistry

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Ecto-enzymes can be defined as membrane-bound proteins that have their active site facing the extracellular millieu. In trypanosomatids, the physiological roles of these enzymes remain to be completed elucidated; however, many important events have already been related to them, such as the survival of parasites during their complex life cycle and the successful establishment of host infection. This chapter focuses on two remarkable classes of ecto-enzymes: ecto-nucleotidases and ecto-phosphatases, summarizing their occurrence and possible physiological roles in Leishmania and Trypanosoma genera. Ecto-nucleotidases are characterized by their ability to hydrolyze extracellular nucleotides, playing an important role in purinergic signaling. By the action of these ecto-enzymes, parasites are capable of modulating the host immune system, which leads to a successful parasite infection. Furthermore, ecto-nucleotidases are also involved in the purine salvage pathway, acting in the generation of nucleosides that are able to cross plasma membrane via specialized transporters. Another important ecto-enzyme present in a vast number of pathogenic organisms is the ecto-phosphatase. These enzymes are able to hydrolyze extracellular phosphorylated substrates, releasing free inorganic phosphate that can be internalized by the cell, crossing the plasma membrane through a Pi-transporter. Ecto-phosphatases are also involved in the invasion and survival of parasite in the host cells. Several alternative functions have been suggested for these enzymes in parasites, such as participation in their proliferation, differentiation, nutrition and protection. In this context, the present chapter provides an overview of recent discoveries related to the occurrence of ecto-nucleotidase and ecto-phosphatase activities in Leishmania and Trypanosoma parasites.

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Leishmania mexicana promastigotes secrete a protein tyrosine phosphatase

Cited by 8 publications

References 41 publications

Different secreted phosphatase activities inLeishmania amazonensis

Different secreted phosphatase activities inLeishmania amazonensis

Finding the Smoking Gun: Protein Tyrosine Phosphatases as Tools and Targets of Unicellular Microorganisms and Viruses

Ecto-nucleotidases and Ecto-phosphatases from Leishmania and Trypanosoma Parasites

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