Cargando…
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...
Autores principales: | , , , , , , , , , , , , |
---|---|
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 |
_version_ | 1782177080643944448 |
---|---|
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. |
format | Text |
id | pubmed-2816222 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT millermalgorzata staphylococcalpknbasthefirstprokaryoticrepresentativeoftheprolinedirectedkinases AT donatstefanie staphylococcalpknbasthefirstprokaryoticrepresentativeoftheprolinedirectedkinases AT rakettesonja staphylococcalpknbasthefirstprokaryoticrepresentativeoftheprolinedirectedkinases AT stehlethilo staphylococcalpknbasthefirstprokaryoticrepresentativeoftheprolinedirectedkinases AT kouwenthijsrhm staphylococcalpknbasthefirstprokaryoticrepresentativeoftheprolinedirectedkinases AT dikssanderh staphylococcalpknbasthefirstprokaryoticrepresentativeoftheprolinedirectedkinases AT dreisbachannette staphylococcalpknbasthefirstprokaryoticrepresentativeoftheprolinedirectedkinases AT reilmanewoud staphylococcalpknbasthefirstprokaryoticrepresentativeoftheprolinedirectedkinases AT gronaukatrin staphylococcalpknbasthefirstprokaryoticrepresentativeoftheprolinedirectedkinases AT becherdorte staphylococcalpknbasthefirstprokaryoticrepresentativeoftheprolinedirectedkinases AT peppelenboschmaikelp staphylococcalpknbasthefirstprokaryoticrepresentativeoftheprolinedirectedkinases AT vandijljanmaarten staphylococcalpknbasthefirstprokaryoticrepresentativeoftheprolinedirectedkinases AT ohlsenknut staphylococcalpknbasthefirstprokaryoticrepresentativeoftheprolinedirectedkinases |