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Staphylococcal PknB as the First Prokaryotic Representative of the Proline-Directed Kinases

In eukaryotic cell types, virtually all cellular processes are under control of proline-directed kinases and especially MAP kinases. Serine/threonine kinases in general were originally considered as a eukaryote-specific enzyme family. However, recent studies have revealed that orthologues of eukaryo...

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Autores principales: Miller, Malgorzata, Donat, Stefanie, Rakette, Sonja, Stehle, Thilo, Kouwen, Thijs R. H. M., Diks, Sander H., Dreisbach, Annette, Reilman, Ewoud, Gronau, Katrin, Becher, Dörte, Peppelenbosch, Maikel P., van Dijl, Jan Maarten, Ohlsen, Knut
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2816222/
https://www.ncbi.nlm.nih.gov/pubmed/20140229
http://dx.doi.org/10.1371/journal.pone.0009057
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author Miller, Malgorzata
Donat, Stefanie
Rakette, Sonja
Stehle, Thilo
Kouwen, Thijs R. H. M.
Diks, Sander H.
Dreisbach, Annette
Reilman, Ewoud
Gronau, Katrin
Becher, Dörte
Peppelenbosch, Maikel P.
van Dijl, Jan Maarten
Ohlsen, Knut
author_facet Miller, Malgorzata
Donat, Stefanie
Rakette, Sonja
Stehle, Thilo
Kouwen, Thijs R. H. M.
Diks, Sander H.
Dreisbach, Annette
Reilman, Ewoud
Gronau, Katrin
Becher, Dörte
Peppelenbosch, Maikel P.
van Dijl, Jan Maarten
Ohlsen, Knut
author_sort Miller, Malgorzata
collection PubMed
description In eukaryotic cell types, virtually all cellular processes are under control of proline-directed kinases and especially MAP kinases. Serine/threonine kinases in general were originally considered as a eukaryote-specific enzyme family. However, recent studies have revealed that orthologues of eukaryotic serine/threonine kinases exist in bacteria. Moreover, various pathogenic species, such as Yersinia and Mycobacterium, require serine/threonine kinases for successful invasion of human host cells. The substrates targeted by bacterial serine/threonine kinases have remained largely unknown. Here we report that the serine/threonine kinase PknB from the important pathogen Staphylococcus aureus is released into the external milieu, which opens up the possibility that PknB does not only phosphorylate bacterial proteins but also proteins of the human host. To identify possible human targets of purified PknB, we studied in vitro phosphorylation of peptide microarrays and detected 68 possible human targets for phosphorylation. These results show that PknB is a proline-directed kinase with MAP kinase-like enzymatic activity. As the potential cellular targets for PknB are involved in apoptosis, immune responses, transport, and metabolism, PknB secretion may help the bacterium to evade intracellular killing and facilitate its growth. In apparent agreement with this notion, phosphorylation of the host-cell response coordinating transcription factor ATF-2 by PknB was confirmed by mass spectrometry. Taken together, our results identify PknB as the first prokaryotic representative of the proline-directed kinase/MAP kinase family of enzymes.
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spelling pubmed-28162222010-02-07 Staphylococcal PknB as the First Prokaryotic Representative of the Proline-Directed Kinases Miller, Malgorzata Donat, Stefanie Rakette, Sonja Stehle, Thilo Kouwen, Thijs R. H. M. Diks, Sander H. Dreisbach, Annette Reilman, Ewoud Gronau, Katrin Becher, Dörte Peppelenbosch, Maikel P. van Dijl, Jan Maarten Ohlsen, Knut PLoS One Research Article In eukaryotic cell types, virtually all cellular processes are under control of proline-directed kinases and especially MAP kinases. Serine/threonine kinases in general were originally considered as a eukaryote-specific enzyme family. However, recent studies have revealed that orthologues of eukaryotic serine/threonine kinases exist in bacteria. Moreover, various pathogenic species, such as Yersinia and Mycobacterium, require serine/threonine kinases for successful invasion of human host cells. The substrates targeted by bacterial serine/threonine kinases have remained largely unknown. Here we report that the serine/threonine kinase PknB from the important pathogen Staphylococcus aureus is released into the external milieu, which opens up the possibility that PknB does not only phosphorylate bacterial proteins but also proteins of the human host. To identify possible human targets of purified PknB, we studied in vitro phosphorylation of peptide microarrays and detected 68 possible human targets for phosphorylation. These results show that PknB is a proline-directed kinase with MAP kinase-like enzymatic activity. As the potential cellular targets for PknB are involved in apoptosis, immune responses, transport, and metabolism, PknB secretion may help the bacterium to evade intracellular killing and facilitate its growth. In apparent agreement with this notion, phosphorylation of the host-cell response coordinating transcription factor ATF-2 by PknB was confirmed by mass spectrometry. Taken together, our results identify PknB as the first prokaryotic representative of the proline-directed kinase/MAP kinase family of enzymes. Public Library of Science 2010-02-04 /pmc/articles/PMC2816222/ /pubmed/20140229 http://dx.doi.org/10.1371/journal.pone.0009057 Text en Miller et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Miller, Malgorzata
Donat, Stefanie
Rakette, Sonja
Stehle, Thilo
Kouwen, Thijs R. H. M.
Diks, Sander H.
Dreisbach, Annette
Reilman, Ewoud
Gronau, Katrin
Becher, Dörte
Peppelenbosch, Maikel P.
van Dijl, Jan Maarten
Ohlsen, Knut
Staphylococcal PknB as the First Prokaryotic Representative of the Proline-Directed Kinases
title Staphylococcal PknB as the First Prokaryotic Representative of the Proline-Directed Kinases
title_full Staphylococcal PknB as the First Prokaryotic Representative of the Proline-Directed Kinases
title_fullStr Staphylococcal PknB as the First Prokaryotic Representative of the Proline-Directed Kinases
title_full_unstemmed Staphylococcal PknB as the First Prokaryotic Representative of the Proline-Directed Kinases
title_short Staphylococcal PknB as the First Prokaryotic Representative of the Proline-Directed Kinases
title_sort staphylococcal pknb as the first prokaryotic representative of the proline-directed kinases
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2816222/
https://www.ncbi.nlm.nih.gov/pubmed/20140229
http://dx.doi.org/10.1371/journal.pone.0009057
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