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Although aPKC\u2013Par6 phosphorylates Lgl at three serine sites to exclude it from the apical domain, aPKC\u2013Par6 and Lgl paradoxically form a stable kinase\u2013substrate complex, with conflicting roles proposed for Par6. We report the structure of human aPKC\u03b9\u2013Par6\u03b1 bound to full-length Llgl1, captured through an aPKC\u03b9 docking site and a Par6\n                    <jats:sup>PDZ<\/jats:sup>\n                    contact. This complex traps a phospho-S663 Llgl1 intermediate bridging between aPKC and Par6, impeding phosphorylation progression. Thus, aPKC\u03b9 is effectively inhibited by Llgl1\n                    <jats:sup>pS663<\/jats:sup>\n                    while Llgl1 is captured by aPKC\u03b9\u2013Par6. Mutational disruption of the Lgl\u2013aPKC interaction impedes complex assembly and Lgl phosphorylation, whereas disrupting the Lgl\u2013Par6\n                    <jats:sup>PDZ<\/jats:sup>\n                    contact promotes complex dissociation and Lgl phosphorylation. We demonstrate a Par6\n                    <jats:sup>PDZ<\/jats:sup>\n                    -regulated substrate capture-and-release model requiring binding by active Cdc42 and the apical partner Crumbs to drive complex disassembly. Our results suggest a mechanism for mutual regulation and spatial control of aPKC\u2013Par6 and Lgl activities.\n                  <\/jats:p>","DOI":"10.1038\/s41594-024-01425-0","type":"journal-article","created":{"date-parts":[[2025,1,6]],"date-time":"2025-01-06T05:02:30Z","timestamp":1736139750000},"page":"729-739","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Capture, mutual inhibition and release mechanism for aPKC\u2013Par6 and its multisite polarity substrate Lgl"],"prefix":"10.1038","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9091-9955","authenticated-orcid":false,"given":"Christopher P.","family":"Earl","sequence":"first","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0279-0336","authenticated-orcid":false,"given":"Mathias","family":"Cobbaut","sequence":"additional","affiliation":[]},{"given":"Andr\u00e9","family":"Barros-Carvalho","sequence":"additional","affiliation":[]},{"given":"Marina E.","family":"Ivanova","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9793-7339","authenticated-orcid":false,"given":"David C.","family":"Briggs","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3525-8231","authenticated-orcid":false,"given":"Eurico","family":"Morais-de-S\u00e1","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5907-6980","authenticated-orcid":false,"given":"Peter J.","family":"Parker","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0975-6325","authenticated-orcid":false,"given":"Neil Q.","family":"McDonald","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2025,1,6]]},"reference":[{"key":"1425_CR1","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1038\/s41580-022-00465-y","volume":"23","author":"CE Buckley","year":"2022","unstructured":"Buckley, C. 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