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蛋白质酪氨酸磷酸酶TbPTP1：控制锥虫生命周期分化的分子开关。

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

作者信息

Szöor Balázs, Wilson Jude, McElhinney Helen, Tabernero Lydia, Matthews Keith R

机构信息

Institute of Immunology and Infection Research, University of Edinburgh, Edinburgh EH9 3JT, Scotland, UK.

出版信息

J Cell Biol. 2006 Oct 23;175(2):293-303. doi: 10.1083/jcb.200605090. Epub 2006 Oct 16.

DOI:10.1083/jcb.200605090
PMID:17043136
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2064570/
Abstract

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.

摘要

非洲锥虫（布氏锥虫）的分化需要在哺乳动物宿主和采采蝇之间转换。在哺乳动物宿主中，寄生虫以增殖性细长型或G0期停滞的粗短型存在。粗短型出现在每次寄生虫血症的高峰期，并会分化为栖息在采采蝇中肠的前循环型。我们鉴定出一种抑制锥虫分化的蛋白酪氨酸磷酸酶（TbPTP1）。与酪氨酸磷酸酶一致，重组TbPTP1表现出预期的底物和抑制剂谱，并且其活性会因可逆氧化而受损。通过RNA干扰或药物抑制使单形血流锥虫中的TbPTP1失活，会在一部分定向细胞中触发向前循环型的自发分化。与此观察结果一致，当酪氨酸磷酸酶活性受到抑制时，均一的粗短型群体同步分化为前循环型。我们的数据提出了一种锥虫发育的新模型，即通过酪氨酸去磷酸化在血流中阻止向前循环型的分化。使用PTP1B抑制剂可能会阻断锥虫的传播。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d5a/2064570/52cfaecee48d/jcb1750293f10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d5a/2064570/685c6f21fc7d/jcb1750293f01.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d5a/2064570/cb5f58c565d1/jcb1750293f03.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d5a/2064570/5d17f3c61405/jcb1750293f05.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d5a/2064570/ed557ffb4fdc/jcb1750293f07.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d5a/2064570/9f63703f9ef8/jcb1750293f08.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d5a/2064570/6bc0c3faac17/jcb1750293f09.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d5a/2064570/52cfaecee48d/jcb1750293f10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d5a/2064570/685c6f21fc7d/jcb1750293f01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d5a/2064570/8464628d779b/jcb1750293f02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d5a/2064570/cb5f58c565d1/jcb1750293f03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d5a/2064570/b5784e961317/jcb1750293f04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d5a/2064570/5d17f3c61405/jcb1750293f05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d5a/2064570/abde38fd7dec/jcb1750293f06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d5a/2064570/ed557ffb4fdc/jcb1750293f07.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d5a/2064570/9f63703f9ef8/jcb1750293f08.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d5a/2064570/6bc0c3faac17/jcb1750293f09.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d5a/2064570/52cfaecee48d/jcb1750293f10.jpg

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