Staphylococcal PknB as the first prokaryotic representative of the proline-directed kinases

Malgorzata Miller*, Stefanie Donat, Sonja Rakette, Thilo Stehle, Thijs R.H.M. Kouwen, Sander H. Diks, Annette Dreisbach, Ewoud Reilman, Katrin Gronau, Dörte Becher, Maikel P. Peppelenbosch, Jan Maarten Van Dijl, Knut Ohlsen

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

41 Citations (Scopus)
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Abstract

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.

Original languageEnglish
Article numbere9057
JournalPLoS ONE
Volume5
Issue number2
DOIs
Publication statusPublished - 4 Feb 2010
Externally publishedYes

Bibliographical note

Funding:
Funding for this work was received from the EU (CEU projects LSHM-CT-2006-019064 and LSHG-CT-2006-037469), the transnational SysMO initiative
through project BACELL SysMO, the European Science Foundation under the EUROCORES Programme EuroSCOPE, grant 04-EScope 01-011 from the Research
Council for Earth and Life Sciences of the Netherlands Organization for Scientific Research, the Top Institute Pharma project T4-213, and the Deutsche
Forschungsgemeinschaft (TR34). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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