A kinase-independent function of PAK is crucial for pathogen-mediated actin remodelling
| Autor: | Joe Tyler, Vikash Singh, Anthony C. Davidson, Peter J. Hume, Vassilis Koronakis |
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| Přispěvatelé: | Hume, Peter [0000-0002-4064-4519], Koronakis, Vassilis [0000-0002-1353-1092], Apollo - University of Cambridge Repository, Tyler, Joe [0000-0003-3940-876X] |
| Rok vydání: | 2021 |
| Předmět: |
Bacterial Diseases
Small interfering RNA Salmonellosis Pathology and Laboratory Medicine Biochemistry Signaling Molecules 0302 clinical medicine Medical Conditions Contractile Proteins Fluorescence Microscopy Cell Signaling Salmonella Guanine Nucleotide Exchange Factors Biology (General) Phosphorylation Cytoskeleton Staining 0303 health sciences Microscopy Kinase Salmonella enterica Light Microscopy Cell Staining Cell biology Bacterial Pathogens Nucleic acids Infectious Diseases Medical Microbiology Salmonella Infections Guanine nucleotide exchange factor Host cytoskeleton Pathogens Cellular Structures and Organelles Signal Transduction Research Article QH301-705.5 Immunology macromolecular substances Biology Microbiology 03 medical and health sciences Enterobacteriaceae Virology Genetics Humans Non-coding RNA Molecular Biology Microbial Pathogens Actin 030304 developmental biology Medicine and health sciences Bacteria Biology and life sciences Tumor Suppressor Proteins Organisms Membrane Proteins Proteins Cell Biology RC581-607 Actin cytoskeleton Actins Gene regulation Research and analysis methods Cytoskeletal Proteins Protein kinase domain p21-Activated Kinases Specimen Preparation and Treatment RNA Parasitology Gene expression Immunologic diseases. Allergy 030217 neurology & neurosurgery Rho Guanine Nucleotide Exchange Factors |
| Zdroj: | PLoS Pathogens PLoS Pathogens, Vol 17, Iss 8, p e1009902 (2021) |
| Popis: | Funder: Isaac Newton Trust; funder-id: http://dx.doi.org/10.13039/501100004815 The p21-activated kinase (PAK) family regulate a multitude of cellular processes, including actin cytoskeleton remodelling. Numerous bacterial pathogens usurp host signalling pathways that regulate actin reorganisation in order to promote Infection. Salmonella and pathogenic Escherichia coli drive actin-dependent forced uptake and intimate attachment respectively. We demonstrate that the pathogen-driven generation of both these distinct actin structures relies on the recruitment and activation of PAK. We show that the PAK kinase domain is dispensable for this actin remodelling, which instead requires the GTPase-binding CRIB and the central poly-proline rich region. PAK interacts with and inhibits the guanine nucleotide exchange factor β-PIX, preventing it from exerting a negative effect on cytoskeleton reorganisation. This kinase-independent function of PAK may be usurped by other pathogens that modify host cytoskeleton signalling and helps us better understand how PAK functions in normal and diseased eukaryotic cells. |
| Databáze: | OpenAIRE |
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