A kinase-independent function of PAK is crucial for pathogen-mediated actin remodelling.

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 a...

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Autores principales:	Anthony Davidson, Joe Tyler, Peter Hume, Vikash Singh, Vassilis Koronakis
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/93a0b6ba9c424c89a08427dfe103051c
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spelling	oai:doaj.org-article:93a0b6ba9c424c89a08427dfe103051c2021-12-02T20:00:14ZA kinase-independent function of PAK is crucial for pathogen-mediated actin remodelling.1553-73661553-737410.1371/journal.ppat.1009902https://doaj.org/article/93a0b6ba9c424c89a08427dfe103051c2021-08-01T00:00:00Zhttps://doi.org/10.1371/journal.ppat.1009902https://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374The 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.Anthony DavidsonJoe TylerPeter HumeVikash SinghVassilis KoronakisPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 17, Iss 8, p e1009902 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Anthony Davidson Joe Tyler Peter Hume Vikash Singh Vassilis Koronakis A kinase-independent function of PAK is crucial for pathogen-mediated actin remodelling.
description	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.
format	article
author	Anthony Davidson Joe Tyler Peter Hume Vikash Singh Vassilis Koronakis
author_facet	Anthony Davidson Joe Tyler Peter Hume Vikash Singh Vassilis Koronakis
author_sort	Anthony Davidson
title	A kinase-independent function of PAK is crucial for pathogen-mediated actin remodelling.
title_short	A kinase-independent function of PAK is crucial for pathogen-mediated actin remodelling.
title_full	A kinase-independent function of PAK is crucial for pathogen-mediated actin remodelling.
title_fullStr	A kinase-independent function of PAK is crucial for pathogen-mediated actin remodelling.
title_full_unstemmed	A kinase-independent function of PAK is crucial for pathogen-mediated actin remodelling.
title_sort	kinase-independent function of pak is crucial for pathogen-mediated actin remodelling.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/93a0b6ba9c424c89a08427dfe103051c
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A kinase-independent function of PAK is crucial for pathogen-mediated actin remodelling.

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