A kinase-independent function of PAK is crucial for pathogen-mediated actin remodelling.
| Autor: | Davidson A; Department of Pathology, University of Cambridge, Cambridge, United Kingdom., Tyler J; Department of Pathology, University of Cambridge, Cambridge, United Kingdom., Hume P; Department of Pathology, University of Cambridge, Cambridge, United Kingdom., Singh V; Department of Pathology, University of Cambridge, Cambridge, United Kingdom., Koronakis V; Department of Pathology, University of Cambridge, Cambridge, United Kingdom. |
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| Jazyk: | angličtina |
| Zdroj: | PLoS pathogens [PLoS Pathog] 2021 Aug 30; Vol. 17 (8), pp. e1009902. Date of Electronic Publication: 2021 Aug 30 (Print Publication: 2021). |
| DOI: | 10.1371/journal.ppat.1009902 |
| Abstrakt: | 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. Competing Interests: The authors have declared that no competing interests exist. |
| Databáze: | MEDLINE |
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