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Protein tyrosine phosphatase TbPTP1: a molecular switch controlling life cycle differentiation in trypanosomes
Differentiation in African trypanosomes (Trypanosoma brucei) entails passage between a mammalian host, where parasites exist as a proliferative slender form or a G0-arrested stumpy form, and the tsetse fly. Stumpy forms arise at the peak of each parasitaemia and are committed to differentiation to p...
Autores principales: | , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2006
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2064570/ https://www.ncbi.nlm.nih.gov/pubmed/17043136 http://dx.doi.org/10.1083/jcb.200605090 |
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author | Szöőr, Balázs Wilson, Jude McElhinney, Helen Tabernero, Lydia Matthews, Keith R. |
author_facet | Szöőr, Balázs Wilson, Jude McElhinney, Helen Tabernero, Lydia Matthews, Keith R. |
author_sort | Szöőr, Balázs |
collection | PubMed |
description | Differentiation in African trypanosomes (Trypanosoma brucei) entails passage between a mammalian host, where parasites exist as a proliferative slender form or a G0-arrested stumpy form, and the tsetse fly. Stumpy forms arise at the peak of each parasitaemia and are committed to differentiation to procyclic forms that inhabit the tsetse midgut. We have identified a protein tyrosine phosphatase (TbPTP1) that inhibits trypanosome differentiation. Consistent with a tyrosine phosphatase, recombinant TbPTP1 exhibits the anticipated substrate and inhibitor profile, and its activity is impaired by reversible oxidation. TbPTP1 inactivation in monomorphic bloodstream trypanosomes by RNA interference or pharmacological inhibition triggers spontaneous differentiation to procyclic forms in a subset of committed cells. Consistent with this observation, homogeneous populations of stumpy forms synchronously differentiate to procyclic forms when tyrosine phosphatase activity is inhibited. Our data invoke a new model for trypanosome development in which differentiation to procyclic forms is prevented in the bloodstream by tyrosine dephosphorylation. It may be possible to use PTP1B inhibitors to block trypanosomatid transmission. |
format | Text |
id | pubmed-2064570 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2006 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-20645702007-11-29 Protein tyrosine phosphatase TbPTP1: a molecular switch controlling life cycle differentiation in trypanosomes Szöőr, Balázs Wilson, Jude McElhinney, Helen Tabernero, Lydia Matthews, Keith R. J Cell Biol Research Articles Differentiation in African trypanosomes (Trypanosoma brucei) entails passage between a mammalian host, where parasites exist as a proliferative slender form or a G0-arrested stumpy form, and the tsetse fly. Stumpy forms arise at the peak of each parasitaemia and are committed to differentiation to procyclic forms that inhabit the tsetse midgut. We have identified a protein tyrosine phosphatase (TbPTP1) that inhibits trypanosome differentiation. Consistent with a tyrosine phosphatase, recombinant TbPTP1 exhibits the anticipated substrate and inhibitor profile, and its activity is impaired by reversible oxidation. TbPTP1 inactivation in monomorphic bloodstream trypanosomes by RNA interference or pharmacological inhibition triggers spontaneous differentiation to procyclic forms in a subset of committed cells. Consistent with this observation, homogeneous populations of stumpy forms synchronously differentiate to procyclic forms when tyrosine phosphatase activity is inhibited. Our data invoke a new model for trypanosome development in which differentiation to procyclic forms is prevented in the bloodstream by tyrosine dephosphorylation. It may be possible to use PTP1B inhibitors to block trypanosomatid transmission. The Rockefeller University Press 2006-10-23 /pmc/articles/PMC2064570/ /pubmed/17043136 http://dx.doi.org/10.1083/jcb.200605090 Text en Copyright © 2006, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Research Articles Szöőr, Balázs Wilson, Jude McElhinney, Helen Tabernero, Lydia Matthews, Keith R. Protein tyrosine phosphatase TbPTP1: a molecular switch controlling life cycle differentiation in trypanosomes |
title | Protein tyrosine phosphatase TbPTP1: a molecular switch controlling life cycle differentiation in trypanosomes |
title_full | Protein tyrosine phosphatase TbPTP1: a molecular switch controlling life cycle differentiation in trypanosomes |
title_fullStr | Protein tyrosine phosphatase TbPTP1: a molecular switch controlling life cycle differentiation in trypanosomes |
title_full_unstemmed | Protein tyrosine phosphatase TbPTP1: a molecular switch controlling life cycle differentiation in trypanosomes |
title_short | Protein tyrosine phosphatase TbPTP1: a molecular switch controlling life cycle differentiation in trypanosomes |
title_sort | protein tyrosine phosphatase tbptp1: a molecular switch controlling life cycle differentiation in trypanosomes |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2064570/ https://www.ncbi.nlm.nih.gov/pubmed/17043136 http://dx.doi.org/10.1083/jcb.200605090 |
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