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...

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Main Authors:	Szöőr, Balázs, Wilson, Jude, McElhinney, Helen, Tabernero, Lydia, Matthews, Keith R.
Format:	Online
Language:	English
Published:	The Rockefeller University Press 2006
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2064570/

id	pubmed-2064570
recordtype	oai_dc
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. 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/).
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Szöőr, Balázs Wilson, Jude McElhinney, Helen Tabernero, Lydia Matthews, Keith R.
spellingShingle	Szöőr, Balázs Wilson, Jude McElhinney, Helen Tabernero, Lydia Matthews, Keith R. Protein tyrosine phosphatase TbPTP1: a molecular switch controlling life cycle differentiation in trypanosomes
author_facet	Szöőr, Balázs Wilson, Jude McElhinney, Helen Tabernero, Lydia Matthews, Keith R.
author_sort	Szöőr, Balázs
title	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_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_sort	protein tyrosine phosphatase tbptp1: a molecular switch controlling life cycle differentiation in trypanosomes
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.
publisher	The Rockefeller University Press
publishDate	2006
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2064570/
_version_	1611406711302651904

Protein tyrosine phosphatase TbPTP1: a molecular switch controlling life cycle differentiation in trypanosomes

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