Polymeric Immunoglobulin Receptor-mediated Invasion of Streptococcus pneumoniae into Host Cells Requires a Coordinate Signaling of SRC Family of Protein-tyrosine Kinases, ERK, and c-Jun N-terminal Kinase

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2010
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Agarwal, Vaibhav
Asmat, Tauseef M.
Hammerschmidt, Sven
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Journal of Biological Chemistry. 2010, 285(46), pp. 35615-35623. ISSN 0021-9258. eISSN 1083-351X. Available under: doi: 10.1074/jbc.M110.172999
Zusammenfassung

Streptococcus pneumoniae are commensals of the human nasopharynx with the capacity to invade mucosal respiratory cells. PspC, a pneumococcal surface protein, interacts with the human polymeric immunoglobulin receptor (pIgR) to promote bacterial adherence to and invasion into epithelial cells. Internalization of pneumococci requires the coordinated action of actin cytoskeleton rearrangements and the retrograde machinery of pIgR. Here, we demonstrate the involvement of Src protein-tyrosine kinases (PTKs), focal adhesion kinase (FAK), extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase (JNK) but not p38 mitogen-activated protein kinases (MAPK) in pneumococcal invasion via pIgR. Pharmacological inhibitors of PTKs and MAPKs and genetic interference with Src PTK and FAK functions caused a significant reduction of pIgR-mediated pneumococcal invasion but did not influence bacterial adhesion to host cells. Furthermore, pneumococcal ingestion by host cells induces activation of ERK1/2 and JNK. In agreement with activated JNK, its target molecule and DNA-binding protein c-Jun was phosphorylated. We also show that functionally active Src PTK is essential for activation of ERK1/2 upon pneumococcal infections. In conclusion, these data illustrate the importance of a coordinated signaling between Src PTKs, ERK1/2, and JNK during PspC-pIgR-mediated uptake of pneumococci by host epithelial cells.

Zusammenfassung in einer weiteren Sprache
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570 Biowissenschaften, Biologie
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Bacterial Signal Transduction, ERK, MAP Kinases (MAPKs), Src, Tyrosine-protein Kinase (Tyrosine Kinase), JNK, Focal Adhesion Kinase, Pneumococci
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ISO 690AGARWAL, Vaibhav, Tauseef M. ASMAT, Nina I. DIERDORF, Christof R. HAUCK, Sven HAMMERSCHMIDT, 2010. Polymeric Immunoglobulin Receptor-mediated Invasion of Streptococcus pneumoniae into Host Cells Requires a Coordinate Signaling of SRC Family of Protein-tyrosine Kinases, ERK, and c-Jun N-terminal Kinase. In: Journal of Biological Chemistry. 2010, 285(46), pp. 35615-35623. ISSN 0021-9258. eISSN 1083-351X. Available under: doi: 10.1074/jbc.M110.172999
BibTex
@article{Agarwal2010-11-12Polym-12572,
  year={2010},
  doi={10.1074/jbc.M110.172999},
  title={Polymeric Immunoglobulin Receptor-mediated Invasion of Streptococcus pneumoniae into Host Cells Requires a Coordinate Signaling of SRC Family of Protein-tyrosine Kinases, ERK, and c-Jun N-terminal Kinase},
  number={46},
  volume={285},
  issn={0021-9258},
  journal={Journal of Biological Chemistry},
  pages={35615--35623},
  author={Agarwal, Vaibhav and Asmat, Tauseef M. and Dierdorf, Nina I. and Hauck, Christof R. and Hammerschmidt, Sven}
}
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