{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T22:14:27Z","timestamp":1791929667111,"version":"4.3.4"},"update-to":[{"DOI":"10.1371\/journal.ppat.1009902","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,9,10]],"date-time":"2021-09-10T00:00:00Z","timestamp":1631232000000}}],"reference-count":52,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2021,8,30]],"date-time":"2021-08-30T00:00:00Z","timestamp":1630281600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["101828\/Z\/13\/Z"],"award-info":[{"award-number":["101828\/Z\/13\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/L008122\/1"],"award-info":[{"award-number":["MR\/L008122\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004815","name":"Isaac Newton Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004815","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>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.<jats:italic>Salmonella<\/jats:italic>and pathogenic<jats:italic>Escherichia coli<\/jats:italic>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 \u03b2-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.<\/jats:p>","DOI":"10.1371\/journal.ppat.1009902","type":"journal-article","created":{"date-parts":[[2021,8,30]],"date-time":"2021-08-30T17:40:00Z","timestamp":1630345200000},"page":"e1009902","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":17,"title":["A kinase-independent function of PAK is crucial for pathogen-mediated actin remodelling"],"prefix":"10.1371","volume":"17","author":[{"given":"Anthony","family":"Davidson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joe","family":"Tyler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4064-4519","authenticated-orcid":true,"given":"Peter","family":"Hume","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vikash","family":"Singh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1353-1092","authenticated-orcid":true,"given":"Vassilis","family":"Koronakis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,8,30]]},"reference":[{"key":"ppat.1009902.ref001","first-page":"20","volume-title":"Gene","author":"R Kumar","year":"2017"},{"key":"ppat.1009902.ref002","article-title":"A tale of two Paks","volume":"100","author":"LE Arias-Romero","year":"2008","journal-title":"Biology of the cell \/ under the auspices of the European Cell Biology Organization"},{"key":"ppat.1009902.ref003","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1038\/367040a0","article-title":"A brain serine\/threonine protein kinase activated by Cdc42 and Rac1","volume":"367","author":"E Manser","year":"1994","journal-title":"Nature"},{"key":"ppat.1009902.ref004","doi-asserted-by":"crossref","first-page":"25070","DOI":"10.1074\/jbc.270.42.25070","article-title":"Molecular cloning of a new member of the p21-Cdc42\/Rac-activated kinase (PAK) family.","volume":"270","author":"E Manser","year":"1995","journal-title":"Journal of Biological Chemistry"},{"key":"ppat.1009902.ref005","doi-asserted-by":"crossref","first-page":"2153","DOI":"10.1128\/MCB.18.4.2153","article-title":"A Conserved Negative Regulatory Region in \u03b1PAK: Inhibition of PAK Kinases Reveals Their Morphological Roles Downstream of Cdc42 and Rac1","volume":"18","author":"Z-S Zhao","year":"1998","journal-title":"Molecular and Cellular Biology"},{"key":"ppat.1009902.ref006","article-title":"Structure of PAK1 in an autoinhibited conformation reveals a multistage activation switch","author":"M Lei","year":"2000","journal-title":"Cell"},{"key":"ppat.1009902.ref007","article-title":"The mechanism of PAK activation. 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