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SAM domain-dependent activity of PfTKL3, an essential tyrosine kinase-like kinase of the human malaria parasite Plasmodiumfalciparum
Over the last decade, several protein kinases inhibitors have reached the market for cancer chemotherapy. The kinomes of pathogens represent potentially attractive targets in infectious diseases. The functions of the majority of protein kinases of Plasmodium falciparum, the parasitic protist respons...
Autores principales: | , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
SP Birkhäuser Verlag Basel
2010
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2933843/ https://www.ncbi.nlm.nih.gov/pubmed/20582613 http://dx.doi.org/10.1007/s00018-010-0434-3 |
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author | Abdi, Abdirahman Eschenlauer, Sylvain Reininger, Luc Doerig, Christian |
author_facet | Abdi, Abdirahman Eschenlauer, Sylvain Reininger, Luc Doerig, Christian |
author_sort | Abdi, Abdirahman |
collection | PubMed |
description | Over the last decade, several protein kinases inhibitors have reached the market for cancer chemotherapy. The kinomes of pathogens represent potentially attractive targets in infectious diseases. The functions of the majority of protein kinases of Plasmodium falciparum, the parasitic protist responsible for the most virulent form of human malaria, remain unknown. Here we present a thorough characterisation of PfTKL3 (PF13_0258), an enzyme that belongs to the tyrosine kinase-like kinase (TKL) group. We demonstrate by reverse genetics that PfTKL3 is essential for asexual parasite proliferation in human erythrocytes. PfTKL3 is expressed in both asexual and gametocytes stages, and in the latter the protein co-localises with cytoskeleton microtubules. Recombinant PfTKL3 displays in vitro autophosphorylation activity and is able to phosphorylate exogenous substrates, and both activities are dramatically dependent on the presence of an N-terminal “sterile α-motif” domain. This study identifies PfTKL3 as a validated drug target amenable to high-throughput screening. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00018-010-0434-3) contains supplementary material, which is available to authorized users. |
format | Text |
id | pubmed-2933843 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | SP Birkhäuser Verlag Basel |
record_format | MEDLINE/PubMed |
spelling | pubmed-29338432010-09-10 SAM domain-dependent activity of PfTKL3, an essential tyrosine kinase-like kinase of the human malaria parasite Plasmodiumfalciparum Abdi, Abdirahman Eschenlauer, Sylvain Reininger, Luc Doerig, Christian Cell Mol Life Sci Research Article Over the last decade, several protein kinases inhibitors have reached the market for cancer chemotherapy. The kinomes of pathogens represent potentially attractive targets in infectious diseases. The functions of the majority of protein kinases of Plasmodium falciparum, the parasitic protist responsible for the most virulent form of human malaria, remain unknown. Here we present a thorough characterisation of PfTKL3 (PF13_0258), an enzyme that belongs to the tyrosine kinase-like kinase (TKL) group. We demonstrate by reverse genetics that PfTKL3 is essential for asexual parasite proliferation in human erythrocytes. PfTKL3 is expressed in both asexual and gametocytes stages, and in the latter the protein co-localises with cytoskeleton microtubules. Recombinant PfTKL3 displays in vitro autophosphorylation activity and is able to phosphorylate exogenous substrates, and both activities are dramatically dependent on the presence of an N-terminal “sterile α-motif” domain. This study identifies PfTKL3 as a validated drug target amenable to high-throughput screening. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00018-010-0434-3) contains supplementary material, which is available to authorized users. SP Birkhäuser Verlag Basel 2010-06-27 2010 /pmc/articles/PMC2933843/ /pubmed/20582613 http://dx.doi.org/10.1007/s00018-010-0434-3 Text en © The Author(s) 2010 https://creativecommons.org/licenses/by-nc/4.0/ This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited. |
spellingShingle | Research Article Abdi, Abdirahman Eschenlauer, Sylvain Reininger, Luc Doerig, Christian SAM domain-dependent activity of PfTKL3, an essential tyrosine kinase-like kinase of the human malaria parasite Plasmodiumfalciparum |
title | SAM domain-dependent activity of PfTKL3, an essential tyrosine kinase-like kinase of the human malaria parasite Plasmodiumfalciparum |
title_full | SAM domain-dependent activity of PfTKL3, an essential tyrosine kinase-like kinase of the human malaria parasite Plasmodiumfalciparum |
title_fullStr | SAM domain-dependent activity of PfTKL3, an essential tyrosine kinase-like kinase of the human malaria parasite Plasmodiumfalciparum |
title_full_unstemmed | SAM domain-dependent activity of PfTKL3, an essential tyrosine kinase-like kinase of the human malaria parasite Plasmodiumfalciparum |
title_short | SAM domain-dependent activity of PfTKL3, an essential tyrosine kinase-like kinase of the human malaria parasite Plasmodiumfalciparum |
title_sort | sam domain-dependent activity of pftkl3, an essential tyrosine kinase-like kinase of the human malaria parasite plasmodiumfalciparum |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2933843/ https://www.ncbi.nlm.nih.gov/pubmed/20582613 http://dx.doi.org/10.1007/s00018-010-0434-3 |
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