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
| Autor: | Vaibhav Agarwal, Sven Hammerschmidt, Christof R. Hauck, Tauseef M. Asmat, Nina I. Dierdorf |
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| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
MAPK/ERK pathway
Biochemistry Bacterial Adhesion Tyrosine-protein Kinase (Tyrosine Kinase) Phosphorylation Extracellular Signal-Regulated MAP Kinases 0303 health sciences Microscopy Confocal Kinase c-jun Receptors Polymeric Immunoglobulin Genistein 3. Good health Cell biology Focal Adhesion Kinase ERK Streptococcus pneumoniae src-Family Kinases Host-Pathogen Interactions Bacterial Signal Transduction MAP Kinases (MAPKs) RNA Interference Signal transduction Proto-oncogene tyrosine-protein kinase Src Signal Transduction Src p38 mitogen-activated protein kinases Blotting Western Biology Transfection Cell Line Focal adhesion 03 medical and health sciences Bacterial Proteins Cell Line Tumor ddc:570 Animals Humans Molecular Biology Protein Kinase Inhibitors 030304 developmental biology Flavonoids 030306 microbiology JNK Mitogen-Activated Protein Kinases Epithelial Cells Cell Biology Enzyme Activation Focal Adhesion Protein-Tyrosine Kinases JNK Pneumococci Polymeric immunoglobulin receptor |
| Zdroj: | Journal of Biological Chemistry Journal of Biological Chemistry; Vol 285 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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