{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T09:44:24Z","timestamp":1789206264201,"version":"build-2803163510"},"reference-count":62,"publisher":"The Company of Biologists","license":[{"start":{"date-parts":[[2020,9,6]],"date-time":"2020-09-06T00:00:00Z","timestamp":1599350400000},"content-version":"vor","delay-in-days":2440,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>Podosomes are integrin-containing adhesion structures commonly found in migrating leukocytes of the monocytic lineage. The actin cytoskeletal organisation of podosomes is based on a WASP-Arp2\/3 mediated mechanism. WASP also associates with a second protein, WIP, where they co-localise in podosome cores. Here we report for the first time that WIP can be phosphorylated on tyrosine residues and that tyrosine phosphorylation of WIP is a trigger for release of WASP from the WIP-WASP complex. Using a knockdown approach together with expression of WIP phosphomimics, we show that in the absence of WIP-WASP binding, cellular WASP is rapidly degraded, leading to disruption of podosomes and a failure of cells to degrade an underlying matrix. In the absence of tyrosine phosphorylation, the WIP-WASP complex remains intact and podosome lifetimes are extended. A screen of candidate kinases and inhibitor-based assays identified Bruton's tyrosine kinase as a regulator of WIP tyrosine phosphorylation. We conclude that tyrosine phosphorylation of WIP is a critical regulator of WASP stability and function as an actin nucleation promoting factor.<\/jats:p>","DOI":"10.1242\/jcs.154880","type":"journal-article","created":{"date-parts":[[2014,11,21]],"date-time":"2014-11-21T05:13:14Z","timestamp":1416546794000},"source":"Crossref","is-referenced-by-count":12,"title":["Tyrosine phosphorylation of WIP releases bound WASP and impairs podosome assembly in macrophages"],"prefix":"10.1242","author":[{"given":"Vineetha","family":"Vijayakumar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Monypenny","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xing Judy","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Machesky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio","family":"Lilla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian J.","family":"Thrasher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"In\u00e9s M.","family":"Ant\u00f3n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yolanda","family":"Calle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gareth E.","family":"Jones","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2014,1,1]]},"reference":[{"key":"2021042614424766000_b1","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1016\/j.ejcb.2005.08.004","article-title":"WIP: a multifunctional protein involved in actin cytoskeleton regulation.","volume":"85","author":"Ant\u00f3n","year":"2006","journal-title":"Eur. 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